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Ajekiigbe VO, Agbo CE, Ogieuhi IJ, Anthony CS, Adewole OA, Ahmed B, Akingbola A, Nwankwo CK, Kayode AT, Chima UE, Adaobi OM. Innovative approaches to treatment of eye diseases: advances in stem cell therapy use in ophthalmology. Int Ophthalmol 2025; 45:113. [PMID: 40120030 DOI: 10.1007/s10792-025-03493-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/06/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION The human eye, a photo-sensory organ with an array of neuronal and tissue networks, remains susceptible to damage from various diseases and disorders despite its being a flawless masterpiece. It is estimated that over 2 billion people suffer from vision loss with common causative factors such as; age-related macular degeneration (AMD), glaucoma, cataracts, diabetic retinopathy, and infections amongst others. The use of Orthodox procedures has only helped mitigate the pathology; however, it doesn't serve any substantial curative purpose. More recently, the incorporation of new therapies via ocular delivery of nanomaterials and stem cell intervention has helped to change tides in the treatment of various ophthalmic pathologies. MAIN TEXT This review provides an overview of the current trends and breakthroughs in ophthalmology via stem cell therapy, with emphasis on its types, mechanisms, applications, and benefits. Mesenchymal stem cells which can arise from embryonic or adult origin possess some immunomodulatory effects that contribute to the therapeutic relevance of the MSCs and the ability to evade rejection from the host. However, the major drawback has been uncontrolled growth which can result in unintended side effects. Moreso, religious and ethical issues concerning the employment of MSCs from embryonic origin have also hindered clinical progression with its use. The use of stem cell therapy in the treatment of eye pathologies which is still undergoing clinical trials has shown to be a more viable treatment approach in ophthalmology as it targets retinal degenerative diseases thereby offering novel pathways for vision restoration. And also serves as a revolutionary alternative for treating severe ocular diseases. Stem cell delivery techniques might be quite cumbersome as the eye is a very delicate organ. The therapeutic interventional technique employed is aimed to ensure the reduction or absence of undesired effects in the deposition of the active pharmaceutical ingredient (API) being the stem cells. Techniques such as hydrogel-based injectables, which offer delivery of the APIs to the desired site of action without change in the physicochemical properties of the drug molecule, the scaffold delivery techniques, and the use of 3D bio-printing which can be used to develop scaffolds for retinal degeneration. The employment of artificial intelligence and machine learning in stem cell therapy has shown to be very fast and efficient in stem cell delivery and preventing likely human errors. CONCLUSIONS Unlike conventional treatments that often focus on managing symptoms, stem cells have the unique ability to repair and regenerate damaged tissues, addressing the root causes of the diseases. However, limitations due to economic, regulatory, and ethical challenges have posed barriers to advancing stem cell therapies.
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Affiliation(s)
| | | | | | | | | | - Bisharat Ahmed
- Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan
| | - Adewunmi Akingbola
- Department of Public Health, University of Cambridge Cambridgeshire Old Trinity Schools, Cambridge, CB2 1TN, England, UK
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Chen Y, Pan Y, Xie Y, Shi Y, Lu Y, Xia Y, Su W, Chen X, Li Z, Wang M, Miao S, Yang Y, Jin C, Luo G, Long S, Xiao H, Huang C, Zhang J, Liang D. Efficacy and safety of minocycline in retinitis pigmentosa: a prospective, open-label, single-arm trial. Signal Transduct Target Ther 2024; 9:339. [PMID: 39627217 PMCID: PMC11615376 DOI: 10.1038/s41392-024-02037-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 10/18/2024] [Accepted: 10/30/2024] [Indexed: 12/06/2024] Open
Abstract
Retinitis pigmentosa (RP) is characterized by progressive photoreceptor cells death accelerated by the proliferation and activation of microglia pathologically. No consensus exists on the treatment. Minocycline is recognized as a microglia inhibitor with great anti-inflammatory and neuro-protective functions. However, efficacy of minocycline in RP patients is lacking. We conducted a prospective, open-label, and single-arm trial, in which daily oral minocycline of 100 mg was administered for 12 months in RP patients with light-adapted 30 Hz flicker electroretinography (ERG) amplitude >0 µV in at least one eye (NCT04068207). The primary outcome was the proportion of participants with improvement in the ERG amplitude at month 12. The secondary outcomes included improvements of the following items: other ERGs amplitudes, visual field, best-corrected visual acuity, contrast sensitivity, color vision, and NEI-VFQ-25. 35 of 288 patients met inclusive criteria were enrolled (median [IQR] age, 36 [31-45] years; 17 female [48.6%]). 32 participants completed all examinations, while 3 participants completed the 12-month online visit via conducting NEI-VFQ-25. The primary outcome showed improvement was 34.3% (12 of 35 [95% CI 19.1-52.2]). Similarly, all secondary outcomes showed improvements. Adverse events were reported in 22 participants (62.9%) and were all resolved without extra medication during the study period. No severe adverse events were recorded. Our findings identified daily oral minocycline of 100 mg for 12 months was beneficial in improving the visual function of RP patients with good safety. This study indicates minocycline may be a promising therapy for RP, but a randomized controlled trial is still needed of further exploration.
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Affiliation(s)
- Yuxi Chen
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yuan Pan
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yanyan Xie
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yuxun Shi
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yao Lu
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yiwen Xia
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Wenru Su
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Xiaoqing Chen
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Zuoyi Li
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Minzhen Wang
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Siyu Miao
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yating Yang
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Chenjin Jin
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Guangwei Luo
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Shixian Long
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Hui Xiao
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Chuangxin Huang
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Jian Zhang
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.
| | - Dan Liang
- Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.
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Kaur G, Bisen S, Singh NK. Nanotechnology in retinal diseases: From disease diagnosis to therapeutic applications. BIOPHYSICS REVIEWS 2024; 5:041305. [PMID: 39512331 PMCID: PMC11540445 DOI: 10.1063/5.0214899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 10/17/2024] [Indexed: 11/15/2024]
Abstract
Nanotechnology has demonstrated tremendous promise in the realm of ocular illnesses, with applications for disease detection and therapeutic interventions. The nanoscale features of nanoparticles enable their precise interactions with retinal tissues, allowing for more efficient and effective treatments. Because biological organs are compatible with diverse nanomaterials, such as nanoparticles, nanowires, nanoscaffolds, and hybrid nanostructures, their usage in biomedical applications, particularly in retinal illnesses, has increased. The use of nanotechnology in medicine is advancing rapidly, and recent advances in nanomedicine-based diagnosis and therapy techniques may provide considerable benefits in addressing the primary causes of blindness related to retinal illnesses. The current state, prospects, and challenges of nanotechnology in monitoring nanostructures or cells in the eye and their application to regenerative ophthalmology have been discussed and thoroughly reviewed. In this review, we build on our previously published review article in 2021, where we discussed the impact of nano-biomaterials in retinal regeneration. However, in this review, we extended our focus to incorporate and discuss the application of nano-biomaterials on all retinal diseases, with a highlight on nanomedicine-based diagnostic and therapeutic research studies.
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Nair PP, Keskar MP, Borghare PT, Dzoagbe HY, Kumar T. The New Era of Therapeutic Strategies for the Management of Retinitis Pigmentosa: A Narrative Review of the Pathomolecular Mechanism for Gene Therapies. Cureus 2024; 16:e66814. [PMID: 39280562 PMCID: PMC11393205 DOI: 10.7759/cureus.66814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 08/11/2024] [Indexed: 09/18/2024] Open
Abstract
Retinitis pigmentosa, or RP, is a group of inherited retinal degenerations involving progressive loss of photoreceptor cells- rods and cones- ultimately causing severe vision loss and blindness. RP, although a very common ailment, continues to be an incurable disease with little to be done medically. However, with the breakthroughs in gene therapy and stem cell transplantation in recent years, a new door has been opened to the treatment of RP. This narrative review summarizes the pathomolecular mechanisms of RP, focusing on the genetic and molecular abnormalities that lead to the process of retinal degeneration. In this section, we talk about the current theories of how RP develops, gene mutations, oxidative stress, and inflammation. We also delve into new therapeutic approaches such as gene therapy, stem cell transplantation and genome surgery, which are designed to either replace or repair the damaged photoreceptors to restore vision and ultimately enhance the life of the RP patient. Another topic covered is the obstacles and research frontiers of these revolutionary treatments. This article is intended to give a complete overview of the molecular processes of RP and the promising treatment strategies that could change the way this devastating disease is treated.
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Affiliation(s)
- Praveena P Nair
- Otolaryngology, Mandsaur Institute of Ayurved Education and Research, Bhunyakhedi, IND
- Otolaryngology, Parul Institute of Ayurved, Parul University, Limda, IND
| | - Manjiri P Keskar
- Otolaryngology, Parul institute of Ayurved, Parul University, Limda, IND
| | - Pramod T Borghare
- Otolaryngology, Mahatma Gandhi Ayurved College Hospital and Research, Wardha, IND
| | - Hellen Y Dzoagbe
- Anatomy, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Tanish Kumar
- Medicine, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Zhang B, Gao S, Liu S, Gong X, Wu J, Zhang Y, Ma L, Sheng L. Regenerative mechanisms of stem cells and their clinical applications for degenerative eye diseases. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2024; 29:42. [PMID: 40224196 PMCID: PMC11992415 DOI: 10.4103/jrms.jrms_358_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 01/14/2024] [Accepted: 03/18/2024] [Indexed: 04/15/2025]
Abstract
There are different types of treatment for eye diseases. Although the majority of eye diseases are curable with primary treatments and surgery, some of degenerative eye damages need regeneration that is not gained by conventional procedures. Stem cells, such as mesenchymal stem cells, human embryonic stem cell-derived retinal pigmented epithelium, and inducible pluripotent stem cells, are now considered one of the most important and safe methods for regeneration of various damaged tissues or organs. However, how will stem cell therapy contribute to regeneration and overcome degenerative eye diseases? This review discusses the regenerative mechanisms, clinical applications, and advantages of different types of stem cells for restoring degenerative eye diseases.
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Affiliation(s)
- Baodong Zhang
- Department of Ophthalmology, Hulun Buir Aier Eye Hospital, Hulunbuir, Inner Mongolia, China
| | - Shusong Gao
- Department of Ophthalmology, Ezhou Central Hospital, Ezhou, Hubei, China
| | - Shibo Liu
- Department of Ophthalmology, Hulun Buir Aier Eye Hospital, Hulunbuir, Inner Mongolia, China
| | - Xuewu Gong
- Department of Ophthalmologic, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Jing Wu
- Department of Ophthalmologic, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Yu Zhang
- Department of Ophthalmologic, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Li Ma
- Department of Ophthalmologic, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Lijie Sheng
- Department of Ophthalmologic, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China
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Vingolo EM, Mascolo S, Miccichè F, Manco G. Retinitis Pigmentosa: From Pathomolecular Mechanisms to Therapeutic Strategies. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:189. [PMID: 38276069 PMCID: PMC10819364 DOI: 10.3390/medicina60010189] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/13/2024] [Accepted: 01/15/2024] [Indexed: 01/27/2024]
Abstract
Retinitis pigmentosa is an inherited disease, in which mutations in different types of genes lead to the death of photoreceptors and the loss of visual function. Although retinitis pigmentosa is the most common type of inherited retinal dystrophy, a clear line of therapy has not yet been defined. In this review, we will focus on the therapeutic aspect and attempt to define the advantages and disadvantages of the protocols of different therapies. The role of some therapies, such as antioxidant agents or gene therapy, has been established for years now. Many clinical trials on different genes and mutations causing RP have been conducted, and the approval of voretigene nepavorec by the FDA has been an important step forward. Nonetheless, even if gene therapy is the most promising type of treatment for these patients, other innovative strategies, such as stem cell transplantation or hyperbaric oxygen therapy, have been shown to be safe and improve visual quality during clinical trials. The treatment of this disease remains a challenge, to which we hope to find a solution as soon as possible.
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Affiliation(s)
| | - Simona Mascolo
- Sense Organs Department, UOSD of Ophtalmology, University la Sapienza of Rome, Polo Pontino-Ospedale A. Fiorini, 4019 Terracina, Italy; (E.M.V.); (F.M.); (G.M.)
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Chen X, Xu N, Li J, Zhao M, Huang L. Stem cell therapy for inherited retinal diseases: a systematic review and meta-analysis. Stem Cell Res Ther 2023; 14:286. [PMID: 37798796 PMCID: PMC10557171 DOI: 10.1186/s13287-023-03526-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 09/28/2023] [Indexed: 10/07/2023] Open
Abstract
PURPOSE Stem cell therapy is a promising therapeutic approach for inherited retinal diseases (IRDs). This study aims to quantitatively examine the effectiveness and safety of stem cell therapy for patients with IRDs, including retinitis pigmentosa and Stargardt disease (STGD). METHODS We searched PubMed, EMBASE, Web of Science, Cochrane Library databases, and the ClinicalTrials.gov website. The latest retrieval time was August 20, 2023. The primary outcomes were rates and mean difference (MD) of best-corrected visual acuity (BCVA) improvement. Subgroup analyses were conducted according to administration routes and stem cell types. This study was registered with PROSPERO (CRD42022349271). RESULTS Twenty-one prospective studies, involving 496 eyes (404 RP and 92 STGD) of 382 patients (306 RP and 76 STGD), were included in this study. For RP, the rate of BCVA improvement was 49% and 30% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months post-treatment (MD = - 0.12 logMAR, 95% CI .17 to - 0.06 logMAR; P < 0.001), while there was no significant difference at 12 months post-treatment (MD = -0.06 logMAR; 95% CI - 0.13 to 0.01 logMAR; P = 0.10). For STGD, the rate of BCVA improvement was 60% and 55% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months (MD = - 0.14 logMAR, 95% CI - 0.22 to - 0.07 logMAR; P = 0.0002) and 12 months (MD = - 0.17 logMAR, 95% CI - 0.29 to - 0.04 logMAR; P = 0.01). Subgroup analyses showed suprachoroidal space injection of stem cells may be more efficient for RP. Eleven treated-related ocular adverse events from three studies and no related systemic adverse events were reported. CONCLUSIONS This study suggests stem cell therapy may be effective and safe for patients with RP or STGD. The long-term vision improvement may be limited for RP patients. Suprachoroidal space injection of stem cells may be a promising administration route for RP patients. Limited by the low grade of evidence, large sample size randomized clinical trials are required in the future.
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Affiliation(s)
- Xiaodong Chen
- Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Ningda Xu
- Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jiarui Li
- Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Mingwei Zhao
- Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Lvzhen Huang
- Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing, China.
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
- College of Optometry, Peking University Health Science Center, Beijing, China.
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Becherucci V, Bacci GM, Marziali E, Sodi A, Bambi F, Caputo R. The New Era of Therapeutic Strategies for the Treatment of Retinitis Pigmentosa: A Narrative Review of Pathomolecular Mechanisms for the Development of Cell-Based Therapies. Biomedicines 2023; 11:2656. [PMID: 37893030 PMCID: PMC10604477 DOI: 10.3390/biomedicines11102656] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/20/2023] [Accepted: 09/25/2023] [Indexed: 10/29/2023] Open
Abstract
Retinitis pigmentosa, defined more properly as cone-rod dystrophy, is a paradigm of inherited diffuse retinal dystrophies, one of the rare diseases with the highest prevalence in the worldwide population and one of the main causes of low vision in the pediatric and elderly age groups. Advancements in and the understanding of molecular biology and gene-editing technologies have raised interest in laying the foundation for new therapeutic strategies for rare diseases. As a consequence, new possibilities for clinicians and patients are arising due to the feasibility of treating such a devastating disorder, reducing its complications. The scope of this review focuses on the pathomolecular mechanisms underlying RP better to understand the prospects of its treatment using innovative approaches.
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Affiliation(s)
- Valentina Becherucci
- Cell Factory Meyer, Children’s Hospital A. Meyer Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Florence, 50139 Florence, Italy; (V.B.); (F.B.)
| | - Giacomo Maria Bacci
- Pediatric Ophthalmology Unit, Children’s Hospital A. Meyer Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Florence, 50139 Florence, Italy; (E.M.); (R.C.)
| | - Elisa Marziali
- Pediatric Ophthalmology Unit, Children’s Hospital A. Meyer Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Florence, 50139 Florence, Italy; (E.M.); (R.C.)
| | - Andrea Sodi
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 50139 Florence, Italy;
| | - Franco Bambi
- Cell Factory Meyer, Children’s Hospital A. Meyer Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Florence, 50139 Florence, Italy; (V.B.); (F.B.)
| | - Roberto Caputo
- Pediatric Ophthalmology Unit, Children’s Hospital A. Meyer Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Florence, 50139 Florence, Italy; (E.M.); (R.C.)
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Wang H, Ouyang W, Liu Y, Zhang M, Zhao H, Wang J, Yin Z. Visual task-related functional and structural magnetic resonance imaging for the objective quantitation of visual function in patients with advanced retinitis pigmentosa. Front Aging Neurosci 2022; 14:825204. [PMID: 36034150 PMCID: PMC9416479 DOI: 10.3389/fnagi.2022.825204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 06/28/2022] [Indexed: 11/22/2022] Open
Abstract
Purpose The objective quantitation of visual function in patients with advanced retinitis pigmentosa (RP) presents a difficult challenge due to the weak visual function of these patients. This study utilized magnetic resonance imaging (MRI) to assess the function and structure of the visual cortex (VC) in patients with RP and quantitatively categorize them. Materials and Methods Twenty-three patients with RP and ten healthy controls (HCs) were enrolled for MRI examinations. The patients were divided into form perception (FP) and no form perception (NFP) groups. Participants underwent structural MRI scans, and two visual task functional MRI scans were performed using stimuli, including white flash and black and white checkerboard patterns. Eight regions of interest (ROIs) were studied. In structural MRI, the gray matter volume (GMV) was compared in the ROIs. In the two visual tasks, the response intensity and functional connectivity (FC) of ROIs were also compared separately. Correlation analysis was performed to explore the correlations between the structural and functional parameters. Results In the structural analysis, the GMV in Brodmann areas 17, 18, and 19 of the FP and NFP groups was significantly lower than that of HCs. Regarding the functional data, the response intensity in the VC of both the FP and NFP groups was significantly lower than that in HCs. The response in Brodmann areas 17, 18, and 19 obtained using the pattern stimulus was significantly lower in the NFP group than in the FP group. For the FC comparison, the FP and NFP groups exhibited significantly lower values in several pathways than the HCs, and FC in the ipsilateral V1–contralateral V1 pathway in the flash task was significantly lower in the NFP group than in the FP group. A positive correlation between response intensity and GMV was observed in Brodmann areas 17, 18, and 19 in both flash and pattern visual tasks. Conclusion Magnetic resonance imaging was an effective tool to objectively and quantitatively evaluate the visual function of patients with advanced RP. Response intensity and FC were effective parameters to distinguish FP and NFP patients. A positive correlation between response intensity and GMV was observed in the VC.
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Affiliation(s)
- Hao Wang
- Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China
- Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China
| | - Wangbin Ouyang
- Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China
- Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China
| | - Yong Liu
- Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China
- Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China
| | - Minfang Zhang
- Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China
- Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China
| | - He Zhao
- Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China
- Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Army Medical University, Chongqing, China
- *Correspondence: Jian Wang,
| | - Zhengqin Yin
- Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China
- Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China
- Zhengqin Yin,
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Stem cell transplantation as a progressing treatment for retinitis pigmentosa. Cell Tissue Res 2022; 387:177-205. [PMID: 35001210 DOI: 10.1007/s00441-021-03551-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 10/27/2021] [Indexed: 11/02/2022]
Abstract
Retinal degenerative diseases such as retinitis pigmentosa (RP) are of the major causes of vision loss in developed countries. Despite the unclear pathophysiology, treatment methods have been investigated vastly in the past decades. This review article mainly discusses the advances in application of stem cell and progenitor transplantation for retinitis pigmentosa. Stem cell sources such as mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, neural stem cells, retinal progenitor cells, and olfactory ensheathing cells are discussed separately in addition to a brief description of two approaches for treatment of early-stage RP, including gene therapy and nutritional therapy.
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11
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Li Y, Li X, Li X, Zeng Z, Strang N, Shu X, Tan Z. Non-neglectable therapeutic options for age-related macular degeneration: A promising perspective from traditional Chinese medicine. JOURNAL OF ETHNOPHARMACOLOGY 2022; 282:114531. [PMID: 34474141 DOI: 10.1016/j.jep.2021.114531] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 08/14/2021] [Accepted: 08/16/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Age-related macular degeneration (AMD) is a chronic neurodegenerative disease which causes irreversible central vision loss among the elderly population. Traditional Chinese Medicine (TCM), including formulas, acupuncture and herbs, has been used in the treatment of AMD for thousands of years and is currently used by many AMD patients around the world. AIM OF THE REVIEW A comprehensive, in-depth literature review examining the use of TCM in the treatment of AMD has yet to be compiled. This review will improve current knowledge relating to the use of TCM and will open new avenues of exploration in developing new drugs for the treatment of AMD. METHODS A literature search of the PubMed database, Web of Science, Google Scholar and China National Knowledge Infrastructure (CNKI) was performed using relevant terms and keywords related to TCM in the treatment of AMD. Related books, PhD and master's theses were also researched. RESULTS The TCM-based interpretation of AMD has been used to establish a theoretical foundation for understanding the effect of TCM formulas and acupuncture on AMD. The possible mechanism of action of common Chinese herbs has also been discussed in detail. CONCLUSION TCM is a promising treatment option of AMD patients. However, lack of rigorous scientific evidence has limited the impact and uptake of TCM therapy. Future research should focus on improving understanding of the mechanism of action and bioactive components of TCM therapies.
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Affiliation(s)
- Yuli Li
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China
| | - Xing Li
- School of Basic Medical Sciences, Shaoyang University, Shaoyang, Hunan, 422000, PR China
| | - Xiaoya Li
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China
| | - Zhihong Zeng
- College of Biological and Environmental Engineering, Changsha University, Changsha, Hunan, 410022, PR China
| | - Niall Strang
- Department of Vision Science, Glasgow Caledonian University, Glasgow, G4 0BA, UK
| | - Xinhua Shu
- School of Basic Medical Sciences, Shaoyang University, Shaoyang, Hunan, 422000, PR China; Department of Vision Science, Glasgow Caledonian University, Glasgow, G4 0BA, UK; Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, UK.
| | - Zhoujin Tan
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China.
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12
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Mannino G, Russo C, Longo A, Anfuso CD, Lupo G, Lo Furno D, Giuffrida R, Giurdanella G. Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases. World J Stem Cells 2021; 13:632-644. [PMID: 34249232 PMCID: PMC8246249 DOI: 10.4252/wjsc.v13.i6.632] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/07/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which surgical or pharmacological therapies produce limited effects. Among stem cells of different sources, mesenchymal stem cells (MSCs) offer several advantages, such as the absence of ethical concerns, easy harvesting, low immunogenicity and reduced tumorigenesis risks. Other than a multipotent differentiation ability, MSCs can release extracellular vesicles conveying proteins, mRNA and microRNA. Thanks to these properties, new therapeutic approaches have been designed for the treatment of various pathologies, including ocular diseases. In this review, the use of different MSCs and different administration strategies are described for the treatment of diabetic retinopathy, glaucoma, and retinitis pigmentosa. In a large number of investigations, positive results have been obtained by in vitro experiments and by MSC administration in animal models. Most authors agree that beneficial effects are likely related to MSC paracrine activity. Based on these considerations, many clinical trials have already been carried out. Overall, although some adverse effects have been described, promising outcomes are reported. It can be assumed that in the near future, safer and more effective protocols will be developed for more numerous clinical applications to improve the quality of life of patients affected by eye diseases.
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Affiliation(s)
- Giuliana Mannino
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy
| | - Cristina Russo
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy
| | - Anna Longo
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy
| | - Carmelina Daniela Anfuso
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy
| | - Gabriella Lupo
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy
| | - Debora Lo Furno
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy.
| | - Rosario Giuffrida
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy
| | - Giovanni Giurdanella
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania 95123, Italy
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13
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Ahani-Nahayati M, Niazi V, Moradi A, Pourjabbar B, Roozafzoon R, Baradaran-Rafii A, Keshel SH. Cell-based therapy for ocular disorders: A promising frontier. Curr Stem Cell Res Ther 2021; 17:147-165. [PMID: 34161213 DOI: 10.2174/1574888x16666210622124555] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/06/2021] [Accepted: 04/19/2021] [Indexed: 11/22/2022]
Abstract
As the ocular disorders causing long-term blindness or optical abnormalities of the ocular tissue affect the quality of life of patients to a large extent, awareness of their corresponding pathogenesis and the earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for development of visual impairment to blindness. Accordingly, stem cells, because of their particular competencies, have gained extensive attention for application in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding mesenchymal stem/stromal cells (MSC), neural stem cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Müller glia, ciliary epithelia-derived stem cells, and retinal pigment epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard, in the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from age-related macular degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the in vivo reports published during the last decade.
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Affiliation(s)
- Milad Ahani-Nahayati
- Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Vahid Niazi
- Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Alireza Moradi
- Department of Physiology, School of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Bahareh Pourjabbar
- Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Reza Roozafzoon
- Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | | | - Saeed Heidari Keshel
- Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
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14
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Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials. Cells 2021; 10:cells10030588. [PMID: 33799995 PMCID: PMC8001847 DOI: 10.3390/cells10030588] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 02/26/2021] [Accepted: 03/02/2021] [Indexed: 12/13/2022] Open
Abstract
Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.
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15
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Kim JY, Park S, Park SH, Lee D, Kim GH, Noh JE, Lee KJ, Kim GJ. Overexpression of pigment epithelium-derived factor in placenta-derived mesenchymal stem cells promotes mitochondrial biogenesis in retinal cells. J Transl Med 2021; 101:51-69. [PMID: 32724163 DOI: 10.1038/s41374-020-0470-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 06/05/2020] [Accepted: 07/12/2020] [Indexed: 01/13/2023] Open
Abstract
Pigment epithelium-derived factor (PEDF) plays a role in protecting retinal pigment epithelial (RPE) cells from oxidative stress (OS), a causative factor of RPE cell death. Genetically modified mesenchymal stem cells (MSCs) can be used to treat critical and incurable retinal diseases. Here, we overexpressed PEDF in placenta-derived MSCs (PD-MSCsPEDF, PEDF+) using a nonviral gene delivery system and evaluated the characteristics of PD-MSCsPEDF and their potential regenerative effects on RPE cells damaged by H2O2-induced OS. PD-MSCsPEDF maintained their stemness, cell surface marker, and differentiation potential characteristics. Compared to naive cells, PD-MSCsPEDF promoted mitochondrial respiration by enhancing biogenesis regulators (e.g., NRF1, PPARGC1A, and TFAM) as well as antioxidant enzymes (e.g., HMOXs, SODs, and GPX1). Compared to OS-damaged RPE cells cocultured with naive cells, OS-damaged RPE cells cocultured with PD-MSCsPEDF showed PEDF upregulation and VEGF downregulation. The expression levels of antioxidant genes and RPE-specific genes, such as RPE65, RGR, and RRH, were significantly increased in RPE cells cocultured with PD-MSCsPEDF. Furthermore, OS-damaged RPE cells cocultured with PD-MSCsPEDF had dramatically enhanced mitochondrial functions, and antiapoptotic effects improved due to cell survival signaling pathways. In the H2O2-induced retinal degeneration rat model, compared to administration of the naive counterpart, intravitreal administration of PD-MSCsPEDF alleviated proinflammatory cytokines and restored retinal structure and function by increasing PEDF expression and decreasing VEGF expression. Intravitreal administration of PD-MSCsPEDF also protected retinal degeneration against OS by increasing antioxidant gene expression and regulating the mitochondrial ROS levels and biogenesis. Taken together, PEDF overexpression in PD-MSCs improved the mitochondrial activities and induced OS-damaged RPE cell regeneration by regulating the oxidative status and mitochondrial biogenesis in vitro and in vivo. These data suggest that genetic modification of PEDF in PD-MSCs might be a new cell therapy for the treatment of retinal degenerative diseases.
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Affiliation(s)
- Jae Yeon Kim
- Department of Biomedical Science, CHA University, Seongnam, 13488, Republic of Korea
| | - Sohae Park
- Department of Biomedical Science, CHA University, Seongnam, 13488, Republic of Korea
| | - So Hyun Park
- Paju 365 Veterinary Medical Center, Paju, 10892, Republic of Korea
| | - Dongsook Lee
- Hamchoon Women's clinic, Research Center of Fertility & Genetics, Seoul, 06643, Republic of Korea
| | - Gyu Hyun Kim
- Neural Circuits Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Jung Eun Noh
- Neural Circuits Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Kea Joo Lee
- Neural Circuits Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Gi Jin Kim
- Department of Biomedical Science, CHA University, Seongnam, 13488, Republic of Korea.
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16
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Haghighat M, Iranbakhsh A, Baharara J, Ebadi M, Sotoodehnejadnematalahi F. Effect of β-carotene on the differentiation potential of ciliary epithelium-derived MSCs isolated from mouse eyes on alginate-based scaffolds. Exp Eye Res 2020; 202:108346. [PMID: 33147471 DOI: 10.1016/j.exer.2020.108346] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 10/13/2020] [Accepted: 10/29/2020] [Indexed: 12/19/2022]
Abstract
Retinal degenerative diseases are considered a major challenge all over the world, and stem cell therapy is a promising approach to restore degenerative cells due to RD. MSCs are multipotent stem cells found in a variety of tissues. They are capable of differentiating into various retinal cell types, so it can be a good candidate for various degenerative disorders like retinal degenerations. β-carotene is an antioxidant that could accelerate the stem cell differentiation while using the proper scaffold. In this study, we evaluated the effect of β-carotene on the differentiation potential of ciliary epithelium-derived MSCs isolated from mouse eyes on alginate-based scaffolds. MSCs were isolated from mouse ciliary epithelium, cultured in DMEM medium supplemented with 10% FBS, and identified by detecting their surface antigens. Three 3D culture systems, alginate, alginate/gelatin, and gelatin hydrogels were prepared, and their structures were checked via SEM. MSCs were cultured on 3D and 2D culture system scaffolds following treated with differentiation medium containing 50 μM β-mercaptoethanol, 1 × minimum essential medium-nonessential amino acids and 20% of knockout serum replacement and β-carotene. MSCs viability and differentiation ability were examined by MTT and ICC, respectively. The expression changes of several retinal specific genes (Nestin, RPE65, and Rhodopsin) were also evaluated by qPCR. Over 80% of cells isolated from mouse ciliary epithelium were positive for MSC-specific markers. The viability rates of MSCs grown on all alginate-based scaffolds were above 70%. MSCs cultured on alginate-based scaffold in the differentiation medium containing β-carotene expressed higher levels of rhodopsin protein compared to a 2D culture. Also, the expressions of Nestin, Rhodopsin, and RPE65 genes were upregulated in β-carotene-treated MSCs grown on alginate-based scaffolds. Our results indicate that the addition of β-carotene to the differentiation medium, along with applying alginate-based scaffolds, could induce higher differentiation in mouse ciliary epithelium-derived MSCs into specialized retinal cells.
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Affiliation(s)
- Mahtab Haghighat
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Alireza Iranbakhsh
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
| | - Javad Baharara
- Department of Biology, Applied Biology Research Center, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Mostafa Ebadi
- Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
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17
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Antioxidant and Biological Properties of Mesenchymal Cells Used for Therapy in Retinitis Pigmentosa. Antioxidants (Basel) 2020; 9:antiox9100983. [PMID: 33066211 PMCID: PMC7602011 DOI: 10.3390/antiox9100983] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/04/2020] [Accepted: 10/09/2020] [Indexed: 02/07/2023] Open
Abstract
Both tissue repair and regeneration are a priority in regenerative medicine. Retinitis pigmentosa (RP), a complex retinal disease characterized by the progressive loss of impaired photoreceptors, is currently lacking effective therapies: this represents one of the greatest challenges in the field of ophthalmological research. Although this inherited retinal dystrophy is still an incurable genetic disease, the oxidative damage is an important pathogenetic element that may represent a viable target of therapy. In this review, we summarize the current neuroscientific evidence regarding the effectiveness of cell therapies in RP, especially those based on mesenchymal cells, and we focus on their therapeutic action: limitation of both oxidative stress and apoptotic processes triggered by the disease and promotion of cell survival. Cell therapy could therefore represent a feasible therapeutic option in RP.
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18
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Limoli PG, Limoli CSS, Morales MU, Vingolo EM. Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects. Restor Neurol Neurosci 2020; 38:223-237. [PMID: 32310198 PMCID: PMC7504992 DOI: 10.3233/rnn-190970] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Purpose: To assess whether treatment with the Limoli Retinal Restoration Technique (LRRT) can be performed in patients with retinitis pigmentosa (RP), grafting the autologous cells in a deep scleral pocket above the choroid of each eye to exert their beneficial effect on the residual retinal cells. Methods: The patients were subjected to a complete ophthalmological examination, including best corrected visual acuity (BCVA), close-up visus measurements, spectral domain-optical coherence tomography (SD-OCT), microperimetry (MY), and electroretinography (ERG). Furthermore, the complete ophthalmological examination was carried out at baseline (T0) and at 6 months (T180) after surgery. The Shapiro–Wilk test was used to assess the normality of distribution of the investigated parameters. A mixed linear regression model was used to analyse the difference in all the studied parameters at T0 and T180, and to compare the mean change between the two groups. All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Results: LRRT treatment was performed in 34 eyes of 25 RP patients recruited for the study. The eyes were classified in two groups on the basis of foveal thickness (FT) assessed by SD-OCT: 14 eyes in Group A (FT≤190μm) and the remaining 20 ones in Group B (FT > 190μm). Although it had not reached the statistical significance, Group B showed a better improvement in BCVA, residual close-up visus and sensitivity than Group A. Conclusions: Previous studies have described the role of LRRT in slowing down retinal degenerative diseases. Consequently, this surgical procedure could improve the clinical and rehabilitative prognostic parameters in RP patients. On the other hand, further clinical research and studies with longer follow-up will be needed to evaluate its efficacy.
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Affiliation(s)
| | | | - Marco Ulises Morales
- Division of Clinical Neurosciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Enzo Maria Vingolo
- Department of Sense Organs, Faculty of Medicine and Odontology, Sapienza University of Rome, p.le A. Moro, Rome, Italy
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19
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Ikelle L, Al-Ubaidi MR, Naash MI. Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions. Front Cell Dev Biol 2020; 8:743. [PMID: 32923439 PMCID: PMC7457054 DOI: 10.3389/fcell.2020.00743] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 07/16/2020] [Indexed: 01/14/2023] Open
Abstract
Stem cells have been part of the biomedical landscape since the early 1960s. However, the translation of stem cells to effective therapeutics have met significant challenges, especially for retinal diseases. The retina is a delicate and complex architecture of interconnected cells that are steadfastly interdependent. Degenerative mechanisms caused by acquired or inherited diseases disrupt this interconnectivity, devastating the retina and causing severe vision loss in many patients. Consequently, retinal differentiation of exogenous and endogenous stem cells is currently being explored as replacement therapies in the debilitating diseases. In this review, we will examine the mechanisms involved in exogenous stem cells differentiation and the challenges of effective integration to the host retina. Furthermore, we will explore the current advancements in trans-differentiation of endogenous stem cells, primarily Müller glia.
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Affiliation(s)
- Larissa Ikelle
- Department of Biomedical Engineering, University of Houston, Houston, TX, United States
| | - Muayyad R Al-Ubaidi
- Department of Biomedical Engineering, University of Houston, Houston, TX, United States
| | - Muna I Naash
- Department of Biomedical Engineering, University of Houston, Houston, TX, United States
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20
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Baradaran-Rafii A, Sarvari M, Alavi-Moghadam S, Payab M, Goodarzi P, Aghayan HR, Larijani B, Rezaei-Tavirani M, Biglar M, Arjmand B. Cell-based approaches towards treating age-related macular degeneration. Cell Tissue Bank 2020; 21:339-347. [PMID: 32157501 DOI: 10.1007/s10561-020-09826-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 03/05/2020] [Indexed: 12/19/2022]
Abstract
Age-related macular degeneration as one of the most common causes of worldwide vision loss needs a proper approach for treatment. Therein, cell therapy and regenerative medicine can hold a great promise to be an effective approach. Accordingly, some preclinical and clinical studies were conducted to search around the therapeutic influence of stem cells in Age-related macular degeneration models and subjects. Hereupon, the purpose of the current review is to discuss the mechanisms of age-related macular degeneration, appropriate animal models along with suitable dosage and route of stem cell administration for its treatment.
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Affiliation(s)
- Alireza Baradaran-Rafii
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Sarvari
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moloud Payab
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Goodarzi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Reza Aghayan
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mahmood Biglar
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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21
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Sheludchenko VM, Budzinskaya MV, Ronzina IA, Smirnova TV. [Effectiveness of new techniques of intraocular stem cells transplantation in the treatment of retinitis pigmentosa]. Vestn Oftalmol 2019; 135:267-271. [PMID: 31691671 DOI: 10.17116/oftalma2019135052267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Retinitis pigmentosa (RP) is a degenerative retinal disease that leads to blindness. Recently, treatment methods based on new technologies have emerged. Among them is stem cells transplantation (SC). PURPOSE To make a systematic evaluation of the results of control clinical studies of cellular technologies for the treatment of RP. MATERIAL AND METHODS The key words - retinitis pigmentosa, stem cells, control study - were used to search literature databases PubMed (250), WOS (172), MEDLINE (32) for the last 5 years. According to preliminary criteria, 88 articles were selected, according to final criteria - 4 articles. A total of 25 patients with RP were found. Control points of the analysis were: baseline, 3 months and 12 months. Methods of analysis (events): visual acuity (VA) and flash electroretinogram (f-ERG). RESULTS There was no VA increase in 15 (60%) of the blind (or with negligible vision of less than 20/1600 ENDRS) patients, and the f-ERG was unrecordable. In 10 patients (40%), VA improved from 0.1 to 0.4 logMAR and the amplitude of f-ERG increased at about 3 months after injection. At 12 months, the effect returned to the baseline values. CONCLUSION The use of SC transplantation technology in RP helps achieve short-term (up to 3 months) positive changes in VA and f-ERG, which depend on the initial stage of RP and do not remain in the final stage. This evokes a question of repeated use of SC transplantation in the same patient.
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Affiliation(s)
- V M Sheludchenko
- Research Institute of Eye Diseases, 11A Rossolimo St., Moscow, Russian Federation, 119021
| | - M V Budzinskaya
- Research Institute of Eye Diseases, 11A Rossolimo St., Moscow, Russian Federation, 119021
| | - I A Ronzina
- Research Institute of Eye Diseases, 11A Rossolimo St., Moscow, Russian Federation, 119021
| | - T V Smirnova
- Research Institute of Eye Diseases, 11A Rossolimo St., Moscow, Russian Federation, 119021
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22
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Chen Y, Yang M, Wang ZJ. (Z)-7,4'-Dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside mitigates retinal degeneration in Rd10 mouse model through inhibiting oxidative stress and inflammatory responses. Cutan Ocul Toxicol 2019; 39:36-42. [PMID: 31648555 DOI: 10.1080/15569527.2019.1685535] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Purpose: As an inherited retinal dystrophy characterised by progressive degeneration of photoreceptor cells, retinitis pigmentosa (RP) leads to partial or total blindness eventually. Possible causes of the photoreceptor cell death are oxidative stress and inflammatory responses. (Z)-7,4'-Dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside (DHAG) is a novel compound with potent antioxidant properties. The aim of this study was to investigate whether DHAG could mitigate photoreceptor cell degeneration in an established mouse model of RP.Materials and method: Rd10 mice were treated with DHAG daily by gavage from postnatal day 12 (P12) to P33. Retinal morphology was evaluated by haematoxylin and eosin staining. Apoptosis-positive cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Oxidative stress markers and inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction, immunostaining and western blot were applied to measure the gene and protein change to explore the underlying mechanisms.Results: Results showed that DHAG significantly preserved the retinal morphology, reducing photoreceptor cell apoptosis, decreasing oxidative stress and inhibiting inflammatory responses in Rd10 mice. The mechanism might be related to inhibit the activation of P38 pathway.Conclusions: This study showed the beneficial effects of DHAG, a compound possessing antioxidant properties, and provided scientific rationale to develop DHAG as a potential agent to treat RP.
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Affiliation(s)
- You Chen
- Department of Ophthalmology, China-Japan Friendship Hospital, Beijing, People's Republic of China
| | - Ming Yang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Zhi-Jun Wang
- Department of Ophthalmology, China-Japan Friendship Hospital, Beijing, People's Republic of China
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Borkowska-Kuczkowska A, Sługocka D, Świątkowska-Flis B, Boruczkowski D. The use of mesenchymal stem cells for the treatment of progressive retinal diseases: a review. Regen Med 2019; 14:321-329. [PMID: 30977436 DOI: 10.2217/rme-2019-0022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Some ocular diseases, such as dystrophies, retinal and macular degeneration, optic nerve atrophy, and Stargardt disease, are progressive and irreversible. In this review, we focus on the use of mesenchymal stem cells (MSCs) in the treatment of these diseases. In animal studies, MSC transplantation significantly delayed retinal degeneration, led to the regeneration of cone cells, and supported the survival of retinal ganglion cells and axon regeneration. In clinical practice, patients with Behcet's disease with retinal vasculitis who received MSC injections experienced a decrease in retinal vasculitis but no improvement in vision acuity. Nonetheless, there is no evidence that MSCs are carcinogenic, and they even reduce the size of tumors in vitro. Furthermore, MSCs do not trigger the immune response.
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Affiliation(s)
- Agnieszka Borkowska-Kuczkowska
- Polish Center of Cell Therapy & Immunotherapy in Częstochowa, Waly Dwernickiego 43/45, 42-202 Częstochowa, Poland.,Agamed Center of Ophthalmology, Jasnogórska 4, 42-202 Częstochowa, Poland
| | - Dominika Sługocka
- Polish Center of Cell Therapy & Immunotherapy in Częstochowa, Waly Dwernickiego 43/45, 42-202 Częstochowa, Poland
| | - Beata Świątkowska-Flis
- Polish Center of Cell Therapy & Immunotherapy in Częstochowa, Waly Dwernickiego 43/45, 42-202 Częstochowa, Poland
| | - Dariusz Boruczkowski
- Polski Bank Komórek Macierzystych SA (FamiCord Group), Jana Pawła II 29, 00-867 Warsaw, Poland
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Colombo L, Montesano G, Sala B, Patelli F, Maltese P, Abeshi A, Bertelli M, Rossetti L. Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study. BMC Ophthalmol 2018; 18:153. [PMID: 29940899 PMCID: PMC6019320 DOI: 10.1186/s12886-018-0817-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 06/08/2018] [Indexed: 12/17/2022] Open
Abstract
Background The aim of this study is to analyze and compare the progression of photoreceptor atrophy among siblings affected by retinitis pigmentosa by means of spectral SD-OCT. Methods Fifty three eyes of 27 patients belonging to 12 family clusters were analyzed. To assess the annual progression rate of photoreceptor atrophy, the ellipsoid zone (EZ) line was measured in OCT sections through the fovea. We used multivariate generalized mixed effects to model the rate of progression and its relation to the initial ellipsoid zone line width. Results During our 4.84 years (± 1.44) mean follow up time (range 3–7) 53 eyes were examined. The ellipsoid zone line width declined with a yearly average rate of 76.4 μm (4.16% / year) (p-value < 0.0001). Progression rates were poorly correlated within family clusters (p-value = 0.23) and showed statistical difference between affected siblings (p-value = 0.007). There was no correlation between inter-familiar progression rate and mode of inheritance (p-value = 0.98) as well as between age and ellipsoid zone line width among siblings (p-value = 0.91). Conclusion RP could be extremely heterogeneous even among siblings: an accurate and sensitive method to follow the progression of the disease is fundamental for future development of clinical trials and therapy strategies.
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Affiliation(s)
- Leonardo Colombo
- Department of Ophthalmology, San Paolo Hospital, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy.
| | - Giovanni Montesano
- Department of Ophthalmology, San Paolo Hospital, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy.,Optometry and Visual Science, School of Health Sciences, City University London, London, UK
| | - Barbara Sala
- Department of Ophthalmology, San Paolo Hospital, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy
| | - Fabio Patelli
- Department of Ophthalmology, San Paolo Hospital, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy
| | - Paolo Maltese
- MAGI Human Medical Genetics Institute, Rovereto, Italy
| | - Andi Abeshi
- MAGI Human Medical Genetics Institute, Rovereto, Italy
| | | | - Luca Rossetti
- Department of Ophthalmology, San Paolo Hospital, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy
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25
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Zhang S, Li J, Li S, Yang Y, Yang M, Yang Z, Zhu X, Zhang L. Targeted next-generation sequencing reveals that a compound heterozygous mutation in phosphodiesterase 6a gene leads to retinitis pigmentosa in a Chinese family. Ophthalmic Genet 2018; 39:487-491. [PMID: 29693493 DOI: 10.1080/13816810.2018.1461912] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Shanshan Zhang
- Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Jie Li
- Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Shujin Li
- Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China
| | - Yeming Yang
- Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Mu Yang
- Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China
| | - Zhenglin Yang
- Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China
- Center of Information in Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Xianjun Zhu
- Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China
- Center of Information in Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Lin Zhang
- Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Center of Information in Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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Mao X, Pan T, Shen H, Xi H, Yuan S, Liu Q. The rescue effect of mesenchymal stem cell on sodium iodate-induced retinal pigment epithelial cell death through deactivation of NF-κB-mediated NLRP3 inflammasome. Biomed Pharmacother 2018; 103:517-523. [PMID: 29677537 DOI: 10.1016/j.biopha.2018.04.038] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 04/04/2018] [Accepted: 04/05/2018] [Indexed: 01/27/2023] Open
Abstract
Age-related macular degeneration (AMD) is a multifactorial disease resulting in the gradual loss of retinal pigment epithelium (RPE) and the permanent visual damage. Various risk factors, including oxidative stress, form a complex network at the confluence of inflammation. Mesenchymal stem cell (MSC) is a well-studied population of adult stem cell with strong neuroprotective and immunoregulatory properties. Here, we reported the protective effect of MSC on sodium iodate (NaIO3)-triggered RPE degeneration. Sodium iodate (NaIO3)-induced RPE cell death was remarkably reduced when cocultured with MSC. Inhibition of several cell death pathways mediated by mitochondrial instability and its subsequent caspase-1/3/8 activation was implicated in this process. In addition, NLRP3 inflammasome, the upstream of caspase-1 activation, was also found downregulated via suppressing its priming signal NF-κB pathway. Taken together, MSC protected against NaIO3-triggered RPE death via deactivating NF-κB-mediated NLRP3 inflammasome and maintaining mitochondrial integrity. This study highlights the significant role of MSC in modulating the proinflammatory environment of AMD, and suggests the clinical value of MSC in treating AMD as well as RPE replacement therapy.
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Affiliation(s)
- Xiying Mao
- Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Ting Pan
- Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Han Shen
- Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Huiyu Xi
- Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Songtao Yuan
- Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Qinghuai Liu
- Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
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Öner A. Stem Cell Treatment in Retinal Diseases: Recent Developments. Turk J Ophthalmol 2018; 48:33-38. [PMID: 29576896 PMCID: PMC5854857 DOI: 10.4274/tjo.89972] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Accepted: 06/07/2017] [Indexed: 12/28/2022] Open
Abstract
Stem cells are undifferentiated cells which have the ability to self-renew and differentiate into mature cells. They are highly proliferative, implying that an unlimited number of mature cells can be generated from a given stem cell source. On this basis, stem cell replacement therapy has been evaluated in recent years as an alternative for various pathologies. Degenerative retinal diseases cause progressive visual decline which originates from continuing loss of photoreceptor cells and outer nuclear layers. Theoretically, this therapy will enable the generation of new retinal cells from stem cells to replace the damaged cells in the diseased retina. In addition, stem cells are able to perform multiple functions, such as immunoregulation, anti-apoptosis of neurons, and neurotrophin secretion. With recent progress in experimental stem cell applications, phase I/II clinical trials have been approved. These latest stem cell transplantation studies showed that this therapy is a promising approach to restore visual function in eyes with degenerative retinal diseases such as retinitis pigmentosa, Stargardts’ macular dystrophy, and age-related macular degeneration. This review focuses on new developments in stem cell therapy for degenerative retinal diseases.
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Affiliation(s)
- Ayşe Öner
- Erciyes University Faculty of Medicine, Department of Ophthalmology, Kayseri, Turkey
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EPIRETINAL MEMBRANE FORMATION AFTER INTRAVITREAL AUTOLOGOUS STEM CELL IMPLANTATION IN A RETINITIS PIGMENTOSA PATIENT. Retin Cases Brief Rep 2018; 11:227-231. [PMID: 27171917 DOI: 10.1097/icb.0000000000000327] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
METHODS A retrospective case report of a retinitis pigmentosa patient who underwent vitrectomy for epiretinal membrane after intravitreal autologous stem cell implantation. RESULTS A 71-year-old female RP patient came to our clinic for ophthalmic evaluation after intravitreal autologous stem cell injection. Four months ago, she underwent intravitreal autologous stem cell injection for both eyes at another hospital. New thick epiretinal membrane (ERM) with extensive macular pucker was found on her left eye. She underwent pars plana vitrectomy and membranectomy. After biopsy, many CD34-positive stem cells were detected in ERM specimen. CONCLUSION This is the first report of ERM formation following intravitreal autologous stem cells injection. CD34-positive stem cells were detected in a human eye at 4 months after injection. Further studies are needed to determine how stem cells caused ERM and how long they would stay in the eye.
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Kang K, Yu M. Protective effect of sulforaphane against retinal degeneration in the Pde6 rd10 mouse model of retinitis pigmentosa. Curr Eye Res 2017; 42:1684-1688. [PMID: 28937835 DOI: 10.1080/02713683.2017.1358371] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE Retinitis pigmentosa (RP) is a group of inherited diseases characterized by the death of rod photoreceptors, followed by the death of cone photoreceptors, progressively leading to partial or complete blindness. Currently no specific treatment is available for RP patients. Sulforaphane (SFN) has been confirmed to be an effective antioxidant in the treatment of many diseases. In this study, we tested the therapeutic effects of SFN against photoreceptor degeneration in Pde6brd10 mice. METHODS rd10 mice and C57/BL6 wild-type (WT) mice were treated with SFN and saline, respectively, from P6 to P20. Electroretinography (ERG), terminal deoxynucleotidyl transferase dUTP nick end labeling and western blot were tested, respectively, at P21 for the analysis of retinal function, retinal cell apoptosis or death and the protein express of GRP78/BiP (TUNEL) as a marker of endoplasmic reticulum (ER) stress. RESULTS Compared with the saline group, the SFN-treated group showed significantly higher ERG a-wave and b-wave amplitudes, less photoreceptor death, and the downregulation of GRP78/BiP. CONCLUSIONS Our data showed that SFN ameliorated the retinal degeneration of rd10 mice, which is possibly related to the downregulation of GRP78 expression.
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Affiliation(s)
- Kai Kang
- a Department of Ophthalmic Research , Cole Eye Institute, Cleveland Clinic Foundation , Cleveland , OH 44195 , USA
| | - Minzhong Yu
- a Department of Ophthalmic Research , Cole Eye Institute, Cleveland Clinic Foundation , Cleveland , OH 44195 , USA.,b Department of Ophthalmology , Cleveland Clinic Lerner College of Medicine of Case Western Reserve University , Cleveland , OH 44195 , USA
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Chen X, Chen Z, Li Z, Zhao C, Zeng Y, Zou T, Fu C, Liu X, Xu H, Yin ZQ. Grafted c-kit +/SSEA1 - eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses. Stem Cell Res Ther 2016; 7:191. [PMID: 28038685 PMCID: PMC5203726 DOI: 10.1186/s13287-016-0451-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 11/25/2016] [Accepted: 12/06/2016] [Indexed: 12/12/2022] Open
Abstract
Background Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry. Methods Eye-wall c-kit+/stage-specific embryonic antigen 1 (SSEA1)− cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kit+/SSEA1− cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test. Results Eye-wall c-kit+/SSEA1− cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kit+/SSEA1− cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kit+/SSEA1− cell-transplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kit+/SSEA1− cells were capable of differentiating into functional photoreceptors that formed new synaptic connections with recipient retinas in rd1 mice. Transplantation also partially corrected the abnormalities of inner retina of rd1 mice. At 4 and 8 weeks post transplantation, the rd1 mice that received c-kit+/SSEA1− cells showed significant increases in a-wave and b-wave amplitude and the percentage of time spent in the dark area. Conclusions Grafted c-kit+/SSEA1− cells restored the retinal function of rd1 mice via regulating neural plasticity and forming new graft-to-host synapses. Electronic supplementary material The online version of this article (doi:10.1186/s13287-016-0451-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xi Chen
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China.,School of Medicine, Nankai University, Tianjin, 300071, China.,Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Zehua Chen
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China
| | - Zhengya Li
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China
| | - Chen Zhao
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China
| | - Yuxiao Zeng
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China
| | - Ting Zou
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China
| | - Caiyun Fu
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China
| | - Xiaoli Liu
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.,Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Haiwei Xu
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China. .,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China.
| | - Zheng Qin Yin
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China. .,Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China.
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Oner A, Gonen ZB, Sinim N, Cetin M, Ozkul Y. Subretinal adipose tissue-derived mesenchymal stem cell implantation in advanced stage retinitis pigmentosa: a phase I clinical safety study. Stem Cell Res Ther 2016; 7:178. [PMID: 27906070 PMCID: PMC5134260 DOI: 10.1186/s13287-016-0432-y] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 07/10/2016] [Accepted: 07/11/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND This prospective clinical case series aimed to investigate the safety of subretinal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in advanced stage retinitis pigmentosa (RP). METHODS This study included 11 patients with end-stage RP who received subretinal implantation of ADMSCs. All patients had a total visual field defect and five of them only had light perception. The best corrected visual acuity (BCVA) in the study was 20/2000. All patients had undetectable electroretinography (ERG). The worst eye of the patient was operated on and, after total vitrectomy with a 23 gauge, ADMSCs were injected subretinally. Patients were evaluated at day 1, at weeks 1-4, and then once a month for 6 months, postoperatively. BCVA, anterior segment and fundus examination, color photography, and optical coherence tomography (OCT) were carried out at each visit. Fundus fluorescein angiography (FFA), perimetry, and ERG recordings were performed before treatment and at the end of month 6, and anytime if necessary during the follow-up. RESULTS All 11 patients completed the 6-month follow-up. None of them had systemic complications. Five patients had no ocular complications. One of the patients experienced choroidal neovascular membrane (CNM) at the implantation site and received an intravitreal anti-vascular endothelial growth factor drug once. Five patients had epiretinal membrane around the transplantation area and at the periphery, and received a second vitrectomy and silicon oil injection. There was no statistically significant difference in BCVA and ERG recordings from baseline. Only one patient experienced an improvement in visual acuity (from 20/2000 to 20/200), visual field, and ERG. Three patients mentioned that the light and some colors were brighter than before and there was a slight improvement in BCVA. The remaining seven patients had no BCVA improvement (five of them only had light perception before surgery). CONCLUSIONS Stem cell treatment with subretinal implantation of ADMSCs seems to have some ocular complications and should be applied with caution. The results of this study provide the first evidence of the short-term safety of ADMSCs in humans, and clarifies the complications of the therapy which would be beneficial for future studies. To optimize the cell delivery technique and to evaluate the effects of this therapy on visual acuity and the quality of life of these patients, future studies with a larger number of cases will be necessary.
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Affiliation(s)
- Ayse Oner
- Department of Ophthalmology, Erciyes University, Kayseri, Turkey
| | - Z. Burcin Gonen
- Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Erciyes University, Kayseri, Turkey
| | - Neslihan Sinim
- Department of Ophthalmology, Erciyes University, Kayseri, Turkey
| | - Mustafa Cetin
- Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
- Department of Internal Medicine, Division of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Yusuf Ozkul
- Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
- Department of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, Turkey
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Abstract
PURPOSE OF REVIEW The following review will provide an update on stem cell therapy with a focus on completed and ongoing human trials. RECENT FINDINGS Significant progress has brought stem cell therapy from proof-of-concept animal models to human clinical trials. Although in its infancy, valuable safety and efficacy data are starting to emerge from trials looking at cell therapies for age-related macular degeneration, Stargardt's macular dystrophy, retinitis pigmentosa, and ischemic retinopathies. SUMMARY Although clinical trials continue to enroll and evaluate stem cell therapy in patients with retinal diseases, preliminary results using both cellular replacement and trophic models have provided initial support for this exciting therapy. Results of these pivotal trials will form a key foundation for moving forward toward the ultimate goal of preventing blinding disease.
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Wide-field optical coherence tomography based microangiography for retinal imaging. Sci Rep 2016; 6:22017. [PMID: 26912261 PMCID: PMC4766473 DOI: 10.1038/srep22017] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 02/03/2016] [Indexed: 12/29/2022] Open
Abstract
Optical coherence tomography angiography (OCTA) allows for the evaluation of functional retinal vascular networks without a need for contrast dyes. For sophisticated monitoring and diagnosis of retinal diseases, OCTA capable of providing wide-field and high definition images of retinal vasculature in a single image is desirable. We report OCTA with motion tracking through an auxiliary real-time line scan ophthalmoscope that is clinically feasible to image functional retinal vasculature in patients, with a coverage of more than 60 degrees of retina while still maintaining high definition and resolution. We demonstrate six illustrative cases with unprecedented details of vascular involvement in retinal diseases. In each case, OCTA yields images of the normal and diseased microvasculature at all levels of the retina, with higher resolution than observed with fluorescein angiography. Wide-field OCTA technology will be an important next step in augmenting the utility of OCT technology in clinical practice.
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Kramerov AA, Ljubimov AV. Stem cell therapies in the treatment of diabetic retinopathy and keratopathy. Exp Biol Med (Maywood) 2015; 241:559-68. [PMID: 26454200 DOI: 10.1177/1535370215609692] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Nonproliferative diabetic retinopathy (DR) is characterized by multiple degenerative changes that could be potentially corrected by stem cell therapies. Most studies so far have attempted to alleviate typical abnormalities of early retinopathy, including vascular hyperpermeability, capillary closure and pericyte dropout. Success was reported with adult stem cells (vascular progenitors or adipose stem cells), as well as induced pluripotent stem cells from cord blood. The cells were able to associate with damaged vessels in both pericyte and endothelial lining positions in models of DR and ischemia-reperfusion. In some diabetic models, functional amelioration of vasculature and electroretinograms was noted. Another approach for endogenous progenitor cell therapy is to normalize dysfunctional diabetic bone marrow and residing endothelial progenitors using NO donors, PPAR-δ and -γ agonists, or inhibition of TGF-β. A potentially important strategy would be to reduce neuropathy by stem cell inoculations, either naïve (e.g., paracrine-acting adipose stem cells) or secreting specific neuroprotectants, such as ciliary neurotrophic factor or brain-derived neurotrophic factor that showed benefit in amyotrophic lateral sclerosis and Parkinson's disease. Recent advances in stem cell therapies for diabetic retinal microangiopathy may form the basis of first clinical trials in the near future. Additionally, stem cell therapies may prove beneficial for diabetic corneal disease (diabetic keratopathy) with pronounced epithelial stem cell dysfunction.
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Affiliation(s)
- Andrei A Kramerov
- Eye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center
| | - Alexander V Ljubimov
- Eye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA
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35
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Scott PA, Kaplan HJ, McCall MA. Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa. Transl Vis Sci Technol 2015; 4:5. [PMID: 26396931 DOI: 10.1167/tvst.4.5.5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 08/12/2015] [Indexed: 01/06/2023] Open
Abstract
PURPOSE Rhodopsin localization and rod photoreceptor (PR) morphology is altered in embryonic transgenic (Tg) Pro23His (P23H) miniswine. At birth, the Tg P23H swine retina lacks rod driven signaling. Curcumin, a neuroprotective food additive, has been shown to rescue Tg P23H rat rod PRs and promote normal trafficking of rhodopsin. We tested the hypothesis that prenatal exposure to curcumin would prevent PR morphological changes in Tg P23H miniswine retinae. METHODS A domestic sow was inseminated with semen from a Tg P23H miniswine founder. Her daily diet was supplemented with curcumin (100 mg/Kg body weight) from embryonic (E) day 80 to E112. The same diet without curcumin was fed to a second inseminated control sow. At E112, 2 days before parturition, both sows were euthanized. Their embryos were harvested, genotyped, and their eyes enucleated and prepared for morphological evaluation. RESULTS In all pigs, we measured mean outer retinal thickness, localization of rhodopsin, and rod PR morphology. Curcumin-treated Tg P23H swine embryonic retinas were similar to WT. Untreated Tg P23H embryonic retinas show significant degenerative effects; their outer retina was thinner, rod PR morphology was abnormal, and rhodopsin was mislocalized to the outer nuclear layer (ONL). CONCLUSIONS These data support a role for curcumin as a neuroprotective agent that prevents/delays morphological abnormalities associated with rod PR degeneration in this Tg P23H swine model of retinitis pigmentosa (RP). TRANSLATIONAL RELEVANCE Curcumin, a Food and Drug Administration-approved dietary supplement, may arrest/delay PR degeneration if ingested by individuals at risk for developing RP.
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Affiliation(s)
- Patrick A Scott
- Departments of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA ; Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA
| | - Henry J Kaplan
- Departments of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA ; Microbiology and Immunology, University of Louisville, Louisville, KY, USA
| | - Maureen A McCall
- Departments of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA ; Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA
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Vecino E, Rodriguez FD, Ruzafa N, Pereiro X, Sharma SC. Glia-neuron interactions in the mammalian retina. Prog Retin Eye Res 2015; 51:1-40. [PMID: 26113209 DOI: 10.1016/j.preteyeres.2015.06.003] [Citation(s) in RCA: 553] [Impact Index Per Article: 55.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 05/18/2015] [Accepted: 06/02/2015] [Indexed: 02/07/2023]
Abstract
The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.
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Affiliation(s)
- Elena Vecino
- Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, Leioa 48940, Vizcaya, Spain
| | - F David Rodriguez
- Department of Biochemistry and Molecular Biology, E-37007, University of Salamanca, Salamanca, Spain
| | - Noelia Ruzafa
- Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, Leioa 48940, Vizcaya, Spain
| | - Xandra Pereiro
- Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, Leioa 48940, Vizcaya, Spain
| | - Sansar C Sharma
- Department of Ophthalmology, Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA; IKERBASQUE, Basque Foundation for Science at Dept. Cell Biology and Histology, UPV/EHU, Spain
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Ben M’Barek K, Regent F, Monville C. Use of human pluripotent stem cells to study and treat retinopathies. World J Stem Cells 2015; 7:596-604. [PMID: 25914766 PMCID: PMC4404394 DOI: 10.4252/wjsc.v7.i3.596] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 11/13/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
Human cell types affected by retinal diseases (such as age-related macular degeneration or retinitis pimentosa) are limited in cell number and of reduced accessibility. As a consequence, their isolation for in vitro studies of disease mechanisms or for drug screening efforts is fastidious. Human pluripotent stem cells (hPSCs), either of embryonic origin or through reprogramming of adult somatic cells, represent a new promising way to generate models of human retinopathies, explore the physiopathological mechanisms and develop novel therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induce pluripotent stem cells together with the continuous improvement of methods to differentiate these cells into disease-affected cellular subtypes opens new perspectives to model and understand a large number of human pathologies, including retinopathies. This review focuses on the added value of hPSCs for the disease modeling of human retinopathies and the study of their molecular pathological mechanisms. We also discuss the recent use of these cells for establishing the validation studies for therapeutic intervention and for the screening of large compound libraries to identify candidate drugs.
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