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1
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Sun GF, Qu XH, Jiang LP, Chen ZP, Wang T, Han XJ. The mechanisms of natural products for eye disorders by targeting mitochondrial dysfunction. Front Pharmacol 2024; 15:1270073. [PMID: 38725662 PMCID: PMC11079200 DOI: 10.3389/fphar.2024.1270073] [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: 07/31/2023] [Accepted: 04/10/2024] [Indexed: 05/12/2024] Open
Abstract
The human eye is susceptible to various disorders that affect its structure or function, including glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction has been identified as a critical factor in the pathogenesis and progression of eye disorders, making it a potential therapeutic target in the clinic. Natural products have been used in traditional medicine for centuries and continue to play a significant role in modern drug development and clinical therapeutics. Recently, there has been a surge in research exploring the efficacy of natural products in treating eye disorders and their underlying physiological mechanisms. This review aims to discuss the involvement of mitochondrial dysfunction in eye disorders and summarize the recent advances in the application of natural products targeting mitochondria. In addition, we describe the future perspective and challenges in the development of mitochondria-targeting natural products.
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Affiliation(s)
- Gui-Feng Sun
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, China
| | - Xin-Hui Qu
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- The Second Department of Neurology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Li-Ping Jiang
- Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, China
| | - Zhi-Ping Chen
- Department of Critical Care Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Tao Wang
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Xiao-Jian Han
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- The Second Department of Neurology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
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2
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Rusciano D, Bagnoli P. Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1334. [PMID: 37512145 PMCID: PMC10383223 DOI: 10.3390/medicina59071334] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/27/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023]
Abstract
In this review, we aim to provide an overview of the recent findings about the treatment of neovascular retinal diseases. The use of conventional drugs and nutraceuticals endowed with antioxidant and anti-inflammatory properties that may support conventional therapies will be considered, with the final aim of achieving risk reduction (prevention) and outcome improvement (cooperation between treatments) of such sight-threatening proliferative retinopathies. For this purpose, we consider a medicinal product one that contains well-defined compound(s) with proven pharmacological and therapeutic effects, usually given for the treatment of full-blown diseases. Rarely are prescription drugs given for preventive purposes. A dietary supplement refers to a compound (often an extract or a mixture) used in the prevention or co-adjuvant treatment of a given pathology. However, it must be kept in mind that drug-supplement interactions may exist and might affect the efficacy of certain drug treatments. Moreover, the distinction between medicinal products and dietary supplements is not always straightforward. For instance, melatonin is formulated as a medicinal product for the treatment of sleep and behavioral problems; at low doses (usually below 1 mg), it is considered a nutraceutical, while at higher doses, it is sold as a psychotropic drug. Despite their lower status with respect to drugs, increasing evidence supports the notion of the beneficial effects of dietary supplements on proliferative retinopathies, a major cause of vision loss in the elderly. Therefore, we believe that, on a patient-by-patient basis, the administration of nutraceuticals, either alone or in association, could benefit many patients, delaying the progression of their disease and likely improving the efficacy of pharmaceutical drugs.
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Affiliation(s)
| | - Paola Bagnoli
- Department of Biology, University of Pisa, 56123 Pisa, Italy
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3
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Ng TK, Chu KO, Wang CC, Pang CP. Green Tea Catechins as Therapeutic Antioxidants for Glaucoma Treatment. Antioxidants (Basel) 2023; 12:1320. [PMID: 37507860 PMCID: PMC10376590 DOI: 10.3390/antiox12071320] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/02/2023] [Accepted: 06/09/2023] [Indexed: 07/30/2023] Open
Abstract
Glaucoma is the leading cause of irreversible blindness and visual impairment, affecting more than 80 million individuals worldwide. Oxidative stress and inflammation-induced neurodegenerative insults to retinal ganglion cells are the main pathogenesis of glaucoma. Retinal ganglion cells, the retinal neurons transmitting the visual signals to the visual cortex in the brain, have very limited regeneration or recovery capacity after damages. Apart from intraocular pressure-lowering treatments, there is still no clinically effective treatment to rescue the degeneration of retinal ganglion cells in glaucoma. Dietary antioxidants are easily accessible and can be applied as supplements assisting in the clinical treatments. Catechins, a chemical family of flavonoids, are the phenolic compounds found in many plants, especially in green tea. The anti-oxidative and anti-inflammatory properties of green tea catechins in vitro and in vivo have been well proven. They could be a potential treatment ameliorating retinal ganglion cell degeneration in glaucoma. In this review, the chemistry, pharmacokinetics, and therapeutic properties of green tea catechins were summarized. Research updates on the biological effects of green tea catechins in cellular and animal experimental glaucoma models were reviewed. In addition, clinical potentials of green tea catechins for glaucoma treatment were also highlighted.
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Affiliation(s)
- Tsz Kin Ng
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou 515041, China
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Kai On Chu
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong
| | - Chi Chiu Wang
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong
| | - Chi Pui Pang
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou 515041, China
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
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Chen Y, Liu Z, Gong Y. Neuron-immunity communication: mechanism of neuroprotective effects in EGCG. Crit Rev Food Sci Nutr 2023; 64:9333-9352. [PMID: 37216484 DOI: 10.1080/10408398.2023.2212069] [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] [Indexed: 05/24/2023]
Abstract
Epigallocatechin gallate (EGCG), a naturally occurring active ingredient unique to tea, has been shown to have neuroprotective potential. There is growing evidence of its potential advantages in the prevention and treatment of neuroinflammation, neurodegenerative diseases, and neurological damage. Neuroimmune communication is an important physiological mechanism in neurological diseases, including immune cell activation and response, cytokine delivery. EGCG shows great neuroprotective potential by modulating signals related to autoimmune response and improving communication between the nervous system and the immune system, effectively reducing the inflammatory state and neurological function. During neuroimmune communication, EGCG promotes the secretion of neurotrophic factors into the repair of damaged neurons, improves intestinal microenvironmental homeostasis, and ameliorates pathological phenotypes through molecular and cellular mechanisms related to the brain-gut axis. Here, we discuss the molecular and cellular mechanisms of inflammatory signaling exchange involving neuroimmune communication. We further emphasize that the neuroprotective role of EGCG is dependent on the modulatory role between immunity and neurology in neurologically related diseases.
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Affiliation(s)
- Ying Chen
- Key Laboratory of Tea Science of Ministry of Educatioxn, Changsha, China
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Changsha, China
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Educatioxn, Changsha, China
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Changsha, China
- Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Changsha, China
- Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops, Ministry of Agriculture and Rural Affairs of China, Hunan Agricultural University, Changsha, China
| | - Yushun Gong
- Key Laboratory of Tea Science of Ministry of Educatioxn, Changsha, China
- National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Changsha, China
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5
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Perdices L, Fuentes-Broto L, Segura F, Cavero A, Orduna-Hospital E, Insa-Sánchez G, Sánchez-Cano AI, Fernández-Sánchez L, Cuenca N, Pinilla I. Systemic epigallocatechin gallate protects against retinal degeneration and hepatic oxidative stress in the P23H-1 rat. Neural Regen Res 2022; 17:625-631. [PMID: 34380903 PMCID: PMC8504391 DOI: 10.4103/1673-5374.320990] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 12/08/2020] [Accepted: 01/13/2021] [Indexed: 11/21/2022] Open
Abstract
Retinitis pigmentosa (RP) is a group of inherited retinal disorders that lead to photoreceptor loss. RP has been reported to be related to oxidative stress, autophagy, and inflammation. (-)-Epigallocatechin gallate (EGCG), the most abundant catechin-based flavonoid in green tea leaves, has significant antioxidant, anti-carcinogenic, antimicrobial, and neuroprotective properties. EGCG, given its low molecular weight and hydrophilic properties, can cross the blood-retinal barrier and is able to reach different ocular tissues such as the lens, cornea, and retina. EGCG has been shown to provide retinal protection against ischemia; sodium nitroprusside-, N-methyl-D-aspartate-, lipopolysaccharide-, light-, sodium iodate-, or H2O2-induced damage and diabetic retinopathy. This suggests that systemic EGCG administration has the potential to protect against retinal degenerative or neurodegenerative diseases such as RP. The aim of this work was to investigate whether EGCG can protect against RP progression in the animal P23H line 1, the model of RP. Albino P23H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical features of RP. Pigmented P23H rats were treated via intraperitoneal injection with saline or EGCG at a dose of 25 mg/kg every week from P100 to P160 and then compared to wild-type Long Evans rats. Rats treated with EGCG showed better visual and retinal electrical function with increased contrast sensitivity and b-wave values compared with those observed in P23H rats treated with vehicle. EGCG reduced lipid peroxidation and increased total antioxidant capacity and catalase and superoxide dismutase activities. No differences were observed in visual acuity, nitrate levels, nitrite levels or glutathione S-transferase activity. In conclusion, EGCG not only reduced the loss of visual function in P23H rats but also improved the levels of antioxidant enzymes and reduced oxidative damage. This study was approved by the Institutional Animal Care and Use Committee (CEICA) from the University of Zaragoza under project license PI12/14 on July 11, 2014.
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Affiliation(s)
- Lorena Perdices
- Aragón Institute for Health Research (IIS Aragón), Zaragoza, Spain
| | - Lorena Fuentes-Broto
- Pharmacology, Physiology & Legal and Forensic Medicine, University of Zaragoza, Zaragoza, Spain
| | - Francisco Segura
- Department of Applied Physics, University of Zaragoza, Zaragoza, Spain
| | - Ana Cavero
- Health Sciences Faculty, San Jorge University, Villanueva de Gállego, Spain
| | | | - Gema Insa-Sánchez
- Pharmacology, Physiology & Legal and Forensic Medicine, University of Zaragoza, Zaragoza, Spain
| | | | - Laura Fernández-Sánchez
- Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
| | - Nicolás Cuenca
- Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
| | - Isabel Pinilla
- Department of Surgery, Gynecology and Obstetrics, University of Zaragoza, Zaragoza, Spain; Department of Ophthalmology, Lozano Blesa University Hospital, Zaragoza, Spain
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6
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Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma. Nutrients 2020; 12:nu12103158. [PMID: 33081127 PMCID: PMC7602834 DOI: 10.3390/nu12103158] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 10/12/2020] [Accepted: 10/14/2020] [Indexed: 12/14/2022] Open
Abstract
Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma.
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Perdices L, Fuentes-Broto L, Segura F, Cuenca N, Orduna-Hospital E, Pinilla I. Epigallocatechin Gallate Slows Retinal Degeneration, Reduces Oxidative Damage, and Modifies Circadian Rhythms in P23H Rats. Antioxidants (Basel) 2020; 9:antiox9080718. [PMID: 32784376 PMCID: PMC7465727 DOI: 10.3390/antiox9080718] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 08/03/2020] [Accepted: 08/06/2020] [Indexed: 12/31/2022] Open
Abstract
Retinitis pigmentosa (RP) includes a group of genetic disorders that involve the loss of visual function due to mutations mainly in photoreceptors but also in other retinal cells. Apoptosis, retinal disorganization, and inflammation are common in the progression of the disease. Epigallocatechin gallate (EGCG) has been proved as beneficial in different eye diseases. Pigmented heterozygous P23H rat was used as an animal model of RP. Visual function was assessed by optomotor and electroretinogram (ERG) and circadian rhythms were evaluated by telemetry. Hepatic oxidative damage and antioxidant defenses were assessed using biochemical tests. The visual function of the EGCG P23H group was preserved, with a deterioration in the activity period and lower values in the interdaily stability parameter. Control rats treated with EGCG were less active than the sham group. EGCG increased antioxidant levels in P23H rats but reduced total hepatic antioxidant capacity by almost 42% in control rats compared to the sham group. We conclude that treatment with EGCG improves visual function and antioxidant status in P23H rats but diminishes antioxidant defenses in wild-type control animals, and slightly worsens activity circadian rhythms. Further studies are necessary to clarify the beneficial effects in disease conditions and in healthy organisms.
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Affiliation(s)
- Lorena Perdices
- Aragon Institute for Health Research (IIS Aragón), 50009 Zaragoza, Spain; (L.P.); (I.P.)
| | - Lorena Fuentes-Broto
- Department of Pharmacology, Physiology and Legal and Forensic Medicine, Universidad de Zaragoza, 50009 Zaragoza, Spain
- Correspondence: ; Tel.: +34-976-761-706
| | - Francisco Segura
- Department of Applied Physics, Universidad de Zaragoza, 50009 Zaragoza, Spain;
| | - Nicolás Cuenca
- Department of Physiology, Genetics and Microbiology, University of Alicante, 03690 San Vicente del Raspeig, Alicante, Spain;
| | | | - Isabel Pinilla
- Aragon Institute for Health Research (IIS Aragón), 50009 Zaragoza, Spain; (L.P.); (I.P.)
- Department of Ophthalmology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
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8
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Rivera-Pérez J, Martínez-Rosas M, Conde-Castañón CA, Toscano-Garibay JD, Ruiz-Pérez NJ, Flores PL, Mera Jiménez E, Flores-Estrada J. Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1. Int J Mol Sci 2020; 21:E3716. [PMID: 32466215 PMCID: PMC7279438 DOI: 10.3390/ijms21103716] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/12/2020] [Accepted: 05/17/2020] [Indexed: 01/20/2023] Open
Abstract
Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with Nrf2/Ho-1 expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0-30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the Ho-1 mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including Ho-1 mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of Ho-1 expression.
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Affiliation(s)
- Josué Rivera-Pérez
- Instituto de Neurobiología, Universidad Nacional Autónoma de Mexico (UNAM), Campus UNAM-Juriquilla, CP 76230 Querétaro, Mexico;
| | - Martín Martínez-Rosas
- Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección 16, Tlalpan, CP 14080 Ciudad de Mexico, Mexico;
| | - César A. Conde-Castañón
- Departamento de Oftalmología, Centro Médico Nacional La Raza, Paseo de las Jacarandas S/N, La Raza, Azcapotzalco, CP 02990 Ciudad de Mexico, Mexico;
| | - Julia D. Toscano-Garibay
- División de Investigación, Hospital Juárez de Mexico, Av. Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, CP 07760 Ciudad de Mexico, Mexico; (J.D.T.-G.); (N.J.R.-P.)
| | - Nancy J. Ruiz-Pérez
- División de Investigación, Hospital Juárez de Mexico, Av. Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, CP 07760 Ciudad de Mexico, Mexico; (J.D.T.-G.); (N.J.R.-P.)
| | - Pedro L. Flores
- Departamento de Instrumentación Electromecánica, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección 16, Tlalpan, CP 14080 Ciudad de Mexico, Mexico;
| | - Elvia Mera Jiménez
- Laboratorio de Cultivo Celular, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomas, Miguel Hidalgo, CP 11340 Ciudad de Mexico, Mexico;
| | - Javier Flores-Estrada
- División de Investigación, Hospital Juárez de Mexico, Av. Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, CP 07760 Ciudad de Mexico, Mexico; (J.D.T.-G.); (N.J.R.-P.)
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9
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Liu XF, Zhou DD, Xie T, Hao JL, Malik TH, Lu CB, Qi J, Pant OP, Lu CW. The Nrf2 Signaling in Retinal Ganglion Cells under Oxidative Stress in Ocular Neurodegenerative Diseases. Int J Biol Sci 2018; 14:1090-1098. [PMID: 29989056 PMCID: PMC6036726 DOI: 10.7150/ijbs.25996] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Accepted: 04/22/2018] [Indexed: 12/28/2022] Open
Abstract
Retinal ganglion cells (RGCs) are one of the important cell types affected in many ocular neurodegenerative diseases. Oxidative stress is considered to be involved in retinal RGCs death in ocular neurodegenerative diseases. More and more attention has been focused on studying the agents that may have neuroprotective effects. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key nuclear transcription factor for the systemic antioxidant defense system. This review elucidates the underlying mechanism of the Nrf2-mediated neuroprotective effects on RGCs in ocular neurodegenerative diseases, such as diabetic retinopathy and retinal ischemia-reperfusion injury. Several Nrf2 inducers that shield RGCs from oxidative stress-induced neurodegeneration via regulating Nrf2 signaling are discussed.
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Affiliation(s)
- Xiu-Fen Liu
- Department of Ophthalmology, The First Hospital of Jilin University, Jilin, China
| | - Dan-Dan Zhou
- Department of Radiology, The First Hospital of Jilin University, Jilin, China
| | - Tian Xie
- Department of . Neurosurgery, The People's Hospital of Jilin Province, Jilin, China
| | - Ji-Long Hao
- Department of Ophthalmology, The First Hospital of Jilin University, Jilin, China
| | - Tayyab Hamid Malik
- Department of Gastroenterology, The First Hospital of Jilin University, Jilin, China
| | - Cheng-Bo Lu
- Department of Cardiology, The First Hospital of Jiamusi University, Heilongjiang, China
| | - Jing Qi
- Department of Ophthalmology, The First Hospital of Jilin University, Jilin, China
| | - Om Prakash Pant
- Department of Ophthalmology, The First Hospital of Jilin University, Jilin, China
| | - Cheng-Wei Lu
- Department of Ophthalmology, The First Hospital of Jilin University, Jilin, China
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10
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He S, Stankowska DL, Ellis DZ, Krishnamoorthy RR, Yorio T. Targets of Neuroprotection in Glaucoma. J Ocul Pharmacol Ther 2017; 34:85-106. [PMID: 28820649 PMCID: PMC5963639 DOI: 10.1089/jop.2017.0041] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 06/08/2017] [Indexed: 12/14/2022] Open
Abstract
Progressive neurodegeneration of the optic nerve and the loss of retinal ganglion cells is a hallmark of glaucoma, the leading cause of irreversible blindness worldwide, with primary open-angle glaucoma (POAG) being the most frequent form of glaucoma in the Western world. While some genetic mutations have been identified for some glaucomas, those associated with POAG are limited and for most POAG patients, the etiology is still unclear. Unfortunately, treatment of this neurodegenerative disease and other retinal degenerative diseases is lacking. For POAG, most of the treatments focus on reducing aqueous humor formation, enhancing uveoscleral or conventional outflow, or lowering intraocular pressure through surgical means. These efforts, in some cases, do not always lead to a prevention of vision loss and therefore other strategies are needed to reduce or reverse the progressive neurodegeneration. In this review, we will highlight some of the ocular pharmacological approaches that are being tested to reduce neurodegeneration and provide some form of neuroprotection.
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Affiliation(s)
- Shaoqing He
- North Texas Eye Research Institute, University of North Texas Health Science Center , Fort Worth, Texas
| | - Dorota L Stankowska
- North Texas Eye Research Institute, University of North Texas Health Science Center , Fort Worth, Texas
| | - Dorette Z Ellis
- North Texas Eye Research Institute, University of North Texas Health Science Center , Fort Worth, Texas
| | - Raghu R Krishnamoorthy
- North Texas Eye Research Institute, University of North Texas Health Science Center , Fort Worth, Texas
| | - Thomas Yorio
- North Texas Eye Research Institute, University of North Texas Health Science Center , Fort Worth, Texas
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11
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Ergün Y. Deney hayvanlarındaki iskemi-reperfüzyon hasarı modellerinde yeşil çayın etkileri. KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNIVERSITESI TIP FAKÜLTESI DERGISI 2017. [DOI: 10.17517/ksutfd.310324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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12
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Fung FKC, Law BYK, Lo ACY. Lutein Attenuates Both Apoptosis and Autophagy upon Cobalt (II) Chloride-Induced Hypoxia in Rat Műller Cells. PLoS One 2016; 11:e0167828. [PMID: 27936094 PMCID: PMC5148028 DOI: 10.1371/journal.pone.0167828] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Accepted: 11/21/2016] [Indexed: 12/17/2022] Open
Abstract
Retinal ischemia/reperfusion injury is a common feature of various retinal diseases such as glaucoma and diabetic retinopathy. Lutein, a potent anti-oxidant, is used to improve visual function in patients with age-related macular degeneration (AMD). Lutein attenuates apoptosis, oxidative stress and inflammation in animal models of acute retinal ischemia/hypoxia. Here, we further show that lutein improved Műller cell viability and enhanced cell survival upon hypoxia-induced cell death through regulation of intrinsic apoptotic pathway. Moreover, autophagy was activated upon treatment of cobalt (II) chloride, indicating that hypoxic injury not only triggered apoptosis but also autophagy in our in vitro model. Most importantly, we report for the first time that lutein treatment suppressed autophagosome formation after hypoxic insult and lutein administration could inhibit autophagic event after activation of autophagy by a pharmacological approach (rapamycin). Taken together, lutein may have a beneficial role in enhancing glial cell survival after hypoxic injury through regulating both apoptosis and autophagy.
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Affiliation(s)
- Frederic K. C. Fung
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R
| | - Betty Y. K. Law
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Amy C. Y. Lo
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R
- Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R
- * E-mail:
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Osmotic Induction of Angiogenic Growth Factor Expression in Human Retinal Pigment Epithelial Cells. PLoS One 2016; 11:e0147312. [PMID: 26800359 PMCID: PMC4723123 DOI: 10.1371/journal.pone.0147312] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 12/31/2015] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Although systemic hypertension is a risk factor of age-related macular degeneration, antihypertensive medications do not affect the risk of the disease. One condition that induces hypertension is high intake of dietary salt resulting in increased blood osmolarity. In order to prove the assumption that, in addition to hypertension, high osmolarity may aggravate neovascular retinal diseases, we determined the effect of extracellular hyperosmolarity on the expression of angiogenic cytokines in cultured human retinal pigment epithelial (RPE) cells. METHODOLOGY/PRINCIPAL FINDINGS Hyperosmolarity was induced by the addition of 100 mM NaCl or sucrose to the culture medium. Hypoxia and oxidative stress were induced by the addition of the hypoxia mimetic CoCl2 and H2O2, respectively. Alterations in gene expression were determined with real-time RT-PCR. Secretion of bFGF was evaluated by ELISA. Cell viability was determined by trypan blue exclusion. Nuclear factor of activated T cell 5 (NFAT5) expression was knocked down with siRNA. Hyperosmolarity induced transcriptional activation of bFGF, HB-EGF, and VEGF genes, while the expression of other cytokines such as EGF, PDGF-A, TGF-β1, HGF, and PEDF was not or moderately altered. Hypoxia induced increased expression of the HB-EGF, EGF, PDGF-A, TGF-β1, and VEGF genes, but not of the bFGF gene. Oxidative stress induced gene expression of HB-EGF, but not of bFGF. The hyperosmotic expression of the bFGF gene was dependent on the activation of p38α/β MAPK, JNK, PI3K, and the transcriptional activity of NFAT5. The hyperosmotic expression of the HB-EGF gene was dependent on the activation of p38α/β MAPK, ERK1/2, and JNK. The hyperosmotic expression of bFGF, HB-EGF, and VEGF genes was reduced by inhibitors of TGF-β1 superfamily activin receptor-like kinase receptors and the FGF receptor kinase, respectively. Hyperosmolarity induced secretion of bFGF that was reduced by inhibition of autocrine/paracrine TGF-β1 signaling and by NFAT5 siRNA, respectively. Hyperosmolarity decreased the viability of the cells; this effect was not altered by exogenous bFGF and HB-EGF. Various vegetable polyphenols (luteolin, quercetin, apigenin) inhibited the hyperosmotic expression of bFGF, HB-EGF, and NFAT5 genes. CONCLUSION Hyperosmolarity induces transcription of bFGF and HB-EGF genes, and secretion of bFGF from RPE cells. This is in part mediated by autocrine/paracrine TGF-β1 and FGF signaling. It is suggested that high intake of dietary salt resulting in osmotic stress may aggravate neovascular retinal diseases via stimulation of the production of angiogenic factors in RPE cells, independent of hypertension.
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Cho H, Hartsock MJ, Xu Z, He M, Duh EJ. Monomethyl fumarate promotes Nrf2-dependent neuroprotection in retinal ischemia-reperfusion. J Neuroinflammation 2015; 12:239. [PMID: 26689280 PMCID: PMC4687295 DOI: 10.1186/s12974-015-0452-z] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 12/04/2015] [Indexed: 12/15/2022] Open
Abstract
Background Retinal ischemia results in neuronal degeneration and contributes to the pathogenesis of multiple blinding diseases. Recently, the fumaric acid ester dimethyl fumarate (DMF) has been FDA-approved for the treatment of multiple sclerosis, based on its neuroprotective and anti-inflammatory effects. Its potential role as a neuroprotective agent for retinal diseases has received little attention. In addition, DMF’s mode of action remains elusive, although studies have suggested nuclear factor erythroid 2-related factor 2 (Nrf2) activation as an important mechanism. Here we investigated the neuroprotective role of monomethyl fumarate (MMF), the biologically active metabolite of DMF, in retinal ischemia-reperfusion (I/R) injury, and examined the role of Nrf2 in mediating MMF action. Methods Wild-type C57BL/6J and Nrf2 knockout (KO) mice were subjected to 90 min of retinal ischemia followed by reperfusion. Mice received daily intraperitoneal injection of MMF. Inflammatory gene expression was measured using quantitative reverse transcription PCR (qRT-PCR) at 48 h after I/R injury. Seven days after I/R, qRT-PCR for Nrf2 target gene expression, immunostaining for Müller cell gliosis and cell loss in the ganglion cell layer (GCL), and electroretinography for retinal function were performed. Results The results of this study confirmed that MMF reduces retinal neurodegeneration in an Nrf2-dependent manner. MMF treatment significantly increased the expression of Nrf2-regulated antioxidative genes, suppressed inflammatory gene expression, reduced Müller cell gliosis, decreased neuronal cell loss in the GCL, and improved retinal function measured by electroretinogram (ERG) after retinal I/R injury in wild-type mice. Importantly, these MMF-mediated beneficial effects were not observed in Nrf2 KO mice. Conclusions These results indicate that fumaric acid esters (FAEs) exert a neuronal protective function in the retinal I/R model and further validate Nrf2 modulation as a major mode of action of FAEs. This suggests that DMF and FAEs could be a potential therapeutic agent for activation of the Nrf2 pathway in retinal and possibly systemic diseases. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0452-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hongkwan Cho
- Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21287, USA.
| | - Matthew J Hartsock
- Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21287, USA.
| | - Zhenhua Xu
- Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21287, USA.
| | - Meihua He
- Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21287, USA.
| | - Elia J Duh
- Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21287, USA.
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Jang H, Choi Y, Ahn HR, Jung SH, Lee CY. Effects of phenolic acid metabolites formed after chlorogenic acid consumption on retinal degeneration in vivo. Mol Nutr Food Res 2015; 59:1918-29. [DOI: 10.1002/mnfr.201400897] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 06/04/2015] [Accepted: 06/26/2015] [Indexed: 12/19/2022]
Affiliation(s)
- Holim Jang
- Department of Food Science; Cornell University; Ithaca NY USA
- Natural Products Research Center; Korea Institute of Science and Technology (KIST); Gangneung Republic of Korea
| | - Yongsoo Choi
- Natural Products Research Center; Korea Institute of Science and Technology (KIST); Gangneung Republic of Korea
| | - Hong Ryul Ahn
- Natural Products Research Center; Korea Institute of Science and Technology (KIST); Gangneung Republic of Korea
| | - Sang Hoon Jung
- Natural Products Research Center; Korea Institute of Science and Technology (KIST); Gangneung Republic of Korea
| | - Chang Yong Lee
- Department of Food Science; Cornell University; Ithaca NY USA
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Qi Y, Chen L, Zhang L, Liu WB, Chen XY, Yang XG. Crocin prevents retinal ischaemia/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K/AKT signalling pathway. Exp Eye Res 2013. [DOI: 10.1016/j.exer.2012.11.011] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Chen F, Jiang L, Shen C, Wan H, Xu L, Wang N, Jonas JB. Neuroprotective effect of epigallocatechin-3-gallate against N-methyl-D-aspartate-induced excitotoxicity in the adult rat retina. Acta Ophthalmol 2012; 90:e609-15. [PMID: 22974415 DOI: 10.1111/j.1755-3768.2012.02502.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has been suggested to reduce glutamate excitotoxicity. We therefore investigated the potentially protective effects of EGCG against N-methyl-d-aspartate (NMDA)-induced excitotoxicity in the retina. METHODS Female Wistar rats (n = 171) were divided into a normal control group (n = 9); saline control group with intravitreal saline injections (n = 54); NMDA control group with an intravitreal NMDA injection and intraperitoneal saline injections (n = 54); and NMDA study group (n = 54) receiving an intravitreal NMDA injection plus intraperitoneal EGCG (25 mg/kg) injections. Starting at 2 days prior to the intravitreal NMDA injection, the intraperitoneal injections were performed daily for the whole study period. At 12 hr, 1, 2, 3 days, 1 and 2 weeks after the intravitreal NMDA injection, the animals were killed. We counted the neurons in the retinal ganglion cell layer (GCL) on histological sections, measured the thickness of Thy-1 immunoreactivity and assessed the expression of Thy-1 mRNA by real-time polymerase chain reaction. RESULTS At all time-points, GCL cell density, thickness of Thy-1 immunoreactivity and expression of Thy-1 mRNA were significantly (all p < 0.05) lower in the NMDA control group than in the NMDA study group, in which the parameters were significantly (all p < 0.05) lower than in the saline control group and the normal control group. In both groups with an intravitreal NMDA injection, GCL cell density, thickness of Thy-1 immunoreactivity and expression of Thy-1 mRNA decreased significantly with increasing follow-up time. CONCLUSIONS Intraperitoneal application of EGCG resulted in a significantly less marked NMDA-associated loss of retinal ganglion cells.
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Affiliation(s)
- Fei Chen
- Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Zhang L, Chong L, Cho J, Liao PC, Shen F, Leung YF. Drug Screening to Treat Early-Onset Eye Diseases: Can Zebrafish Expedite the Discovery? ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY (PHILADELPHIA, PA.) 2012; 1:374-83. [PMID: 26107731 DOI: 10.1097/apo.0b013e31827a9969] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The molecular basis of many early-onset eye diseases has been uncovered, but the number of available drug treatments for improving deteriorated vision is still scarce. Consequently, there is a high demand for new drugs to treat these diseases. This review first provides a brief synopsis of the use of zebrafish model for screening drugs with vision benefits. In particular, visual-motor response, the activity response of larvae to a change in light stimuli, is proposed to serve as a simple and efficient tool for screening drugs that may improve vision in various zebrafish visual mutants. The second part of the review discusses the identification of novel drug candidates, with particular emphasis on naturally derived chemicals including traditional Chinese medicines and nutritional therapies on retinal degenerative diseases. Many of these chemicals have been used in neuroprotection and/or have been consumed by many populations for good health and vision; thus, the screening of these chemicals with various zebrafish visual mutants would expedite the development of novel drugs for treating early-onset eye diseases.
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Affiliation(s)
- Liyun Zhang
- From the *Department of Biological Sciences, Purdue University; and †Department of Biochemistry and Molecular Biology, Indiana University School of Medicine Lafayette, West Lafayette, IN
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Abstract
Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low homeostatic responses which, with time, induce injury to the tissue due to cell loss by apoptosis. In this respect, retinal ischemia is a primary cause of neuronal death. It can be considered as a sort of final common pathway in retinal diseases and results in irreversible morphological and functional changes. This review summarizes the recent knowledge on the effects of ischemia in retinal tissue and points out experimental strategies/models performed to gain better comprehension of retinal ischemia diseases. In particular, the nature of the mechanisms leading to neuronal damage (i.e., excess of glutamate release, oxidative stress and inflammation) will be outlined as well as the potential and most intriguing retinoprotective approaches and the possible therapeutic use of naturally occurring molecules such as neuropeptides. There is a general agreement that a better understanding of the fundamental pathophysiology of retinal ischemia will lead to better management and improved clinical outcome. In this respect, to contrast this pathological state, specific pharmacological strategies need to be developed aimed at the many putative cascades generated during ischemia.
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Chang ZY, Lu DW, Yeh MK, Chiang CH. A novel high-content flow cytometric method for assessing the viability and damage of rat retinal ganglion cells. PLoS One 2012; 7:e33983. [PMID: 22457807 PMCID: PMC3311554 DOI: 10.1371/journal.pone.0033983] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2011] [Accepted: 02/20/2012] [Indexed: 01/04/2023] Open
Abstract
Purpose The aim of the study was to develop a high-content flow cytometric method for assessing the viability and damage of small, medium, and large retinal ganglion cells (RGCs) in N-methyl-D-aspartic acid (NMDA)-injury model. Methods/Results Retinal toxicity was induced in rats by intravitreal injection of NMDA and RGCs were retrogradely labeled with Fluoro-Gold (FG). Seven days post-NMDA injection, flatmount and flow cytometric methods were used to evaluate RGCs. In addition, the RGC area diameter (D(a)) obtained from retinal flatmount imaging were plotted versus apparent volume diameter (D(v)) obtained from flow cytometry for the same cumulative cell number (sequentially from small to large RGCs) percentile (Q) to establish their relationship for accurately determining RGC sizes. Good correlation (r = 0.9718) was found between D(a) and apparent D(v). Both flatmount and flow cytometric analyses of RGCs showed that 40 mM NMDA significantly reduced the numbers of small and medium RGCs but not large RGCs. Additionally, flow cytometry showed that the geometric means of FG and thy-1 intensities in three types of RGCs decreased to 90.96±2.24% (P<0.05) and 91.78±1.89% (P>0.05) for small, 69.62±2.11% (P<0.01) and 69.07±2.98% (P<0.01) for medium, and 69.68±6.48% (P<0.05) and 69.91±6.23% (P<0.05) for large as compared with the normal RGCs. Conclusion The established flow cytometric method provides high-content analysis for differential evaluation of RGC number and status and should be useful for the evaluation of various models of optic nerve injury and the effects of potential neuroprotective agents.
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Affiliation(s)
- Zhi-Yang Chang
- Graduate Institute of Life Sciences, National Defense Medical Center, Neihu, Taipei, Taiwan
| | - Da-Wen Lu
- Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Neihu, Taipei, Taiwan
| | - Ming-Kung Yeh
- Institute of Preventive Medicine, National Defense Medical Center, Sanhsia, Taipei, Taiwan
| | - Chiao-Hsi Chiang
- Graduate Institute of Life Sciences, National Defense Medical Center, Neihu, Taipei, Taiwan
- School of Pharmacy, National Defense Medical Center, Neihu, Taipei, Taiwan
- * E-mail:
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Choi JI, Kim WM, Lee HG, Kim YO, Yoon MH. Role of neuronal nitric oxide synthase in the antiallodynic effects of intrathecal EGCG in a neuropathic pain rat model. Neurosci Lett 2012; 510:53-7. [PMID: 22249118 DOI: 10.1016/j.neulet.2011.12.070] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2011] [Revised: 12/29/2011] [Accepted: 12/30/2011] [Indexed: 12/17/2022]
Abstract
Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, is known to have antioxidant activity against nitric oxide (NO) by scavenging free radicals, chelating metal ions, and inducing endogenous antioxidant enzymes. NO and NO synthase (NOS) play an important role in nociceptive processing. In this study, we examined the effects of intrathecal EGCG in neuropathic pain induced by spinal nerve ligation and the possible involvement of NO. Intrathecal EGCG attenuated mechanical allodynia in spinal nerve ligated-rats, compared to sham-operated rats, with a maximal possible effect of 69.2%. This antinociceptive effect was reversed by intrathecal pretreatment with l-arginine, a precursor of NO. Intrathecal EGCG also blocked the increase in nNOS expression in the spinal cord of spinal nerve-ligated rats, but iNOS expression was not significantly suppressed. These findings suggest that intrathecal EGCG could produce an antiallodynic effect against spinal nerve ligation-induced neuropathic pain, mediated by blockade of nNOS protein expression and inhibition of the pronociceptive effects of NO.
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Affiliation(s)
- Jeong Il Choi
- Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea
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Majumdar S, Srirangam R. Potential of the bioflavonoids in the prevention/treatment of ocular disorders. J Pharm Pharmacol 2010; 62:951-65. [PMID: 20663029 DOI: 10.1211/jpp.62.08.0001] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Flavonoids are a common group of plant polyphenols that give colour and flavour to fruits and vegetables. In recent years, flavonoids have gained importance in the pharmaceutical field through their beneficial effects on human health and are widely available as nutritional supplements. Several pharmacological actions of the bioflavonoids may be useful in the prevention or treatment of ocular diseases responsible for vision loss such as diabetic retinopathy, macular degeneration and cataract. This review aims to summarize the potential therapeutic applications of various bioflavonoids in different ocular diseases and also discusses delivery of these agents to the ocular tissues. KEY FINDINGS It is apparent that the flavonoids are capable of acting on various mechanisms or aetiological factors responsible for the development of different sight threatening ocular diseases. From a drug delivery perspective, ocular bioavailability depends on the physicochemical and biopharmaceutical characteristics of the selected flavonoids and very importantly the route of administration. SUMMARY The potential therapeutic applications of various bioflavonoids in ocular diseases is reviewed and the delivery of these agents to the ocular tissues is discussed. Whereas oral administration of bioflavonoids may demonstrate some pharmacological activity in the outer sections of the posterior ocular segment, protection of the retinal ganglionic cells in vivo may be limited by this delivery route. Systemic or local administration of these agents may yield much higher and effective concentrations of the parent bioflavonoids in the ocular tissues and at much lower doses.
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Affiliation(s)
- Soumyajit Majumdar
- Department of Pharmaceutics, The University of Mississippi, MS 38677, USA.
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Chronic green tea catechins administration prevents oxidative stress-related brain aging in C57BL/6J mice. Brain Res 2010; 1353:28-35. [DOI: 10.1016/j.brainres.2010.07.074] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2010] [Revised: 07/10/2010] [Accepted: 07/21/2010] [Indexed: 11/23/2022]
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Xie J, Jiang L, Zhang T, Jin Y, Yang D, Chen F. Neuroprotective effects of Epigallocatechin-3-gallate (EGCG) in optic nerve crush model in rats. Neurosci Lett 2010; 479:26-30. [PMID: 20471452 DOI: 10.1016/j.neulet.2010.05.020] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2010] [Accepted: 05/07/2010] [Indexed: 02/07/2023]
Abstract
Epigallocatechin-3-gallate (EGCG), the major catechin found in green tea, is a powerful antioxidant and has anti-inflammatory with neuroprotective potential. This study aims to investigate the neuroprotective effects of EGCG in an optic nerve crush (ONC) model in rats. Seventy-two Wistar rats were randomly divided into four groups: normal control (group A), sham operation+EGCG (group B), ONC+vehicle (group C), and ONC+EGCG (group D). The rats were treated intraperitoneally and orally with either vehicle or EGCG (25 mg/kg, injected daily for 5 days and 2 mg/kg orally daily afterwards). Two days after the first injection, an ONC injury was performed by using a micro optic nerve clipper with 40 g power at approximately 2 mm from the optic nerve head for 60 s. Fluorogold was injected into the bilateral superior colliculi 5 days before sacrifice and fluorescent gold-labelled retinal ganglion cells (RGCs) were counted under fluorescence microscopy on days 7, 14 and 28 after ONC. The expression of Neurofilament triplet L (NF-L) was measured via immunohistochemical and Western blotting analysis. In group C, a progressive loss of RGCs was observed after ONC. In contrast, the density of RGCs was significantly higher in group D (p=0.009, independent samples t-test) on day 7 after ONC, and statistical differences were obtained on days 14 and 28 (p=0.026 and p=0.019, respectively, independent samples t-test). The results of immunohistochemical and Western blotting analysis showed significantly higher NF-L protein expression in group D in comparison with group C on days 7, 14 and 28 after ONC. These findings suggest that there are protective effects of EGCG on RGCs after ONC, indicating EGCG might be a potential therapeutic agent for optic nerve diseases.
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Affiliation(s)
- Jun Xie
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
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Akhlaghi M, Bandy B. Dietary green tea extract increases phase 2 enzyme activities in protecting against myocardial ischemia-reperfusion. Nutr Res 2010; 30:32-9. [PMID: 20116658 DOI: 10.1016/j.nutres.2009.11.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2009] [Revised: 11/12/2009] [Accepted: 11/13/2009] [Indexed: 11/19/2022]
Abstract
Green tea catechins are dietary antioxidant compounds that have been shown to protect against myocardial ischemia-reperfusion (IR) injury. Considering reports that catechins can induce phase 2 enzymes in cultured cells and some organs, we hypothesized that part of the protection to heart against IR injury may involve elevation of phase 2 enzyme activities. Rats were fed for 10 days with either control diet (sham and control groups) or the diet mixed with 0.25% green tea extract. At the end of 10 days, hearts were excised and subjected to global ischemia for 20 min followed by reperfusion for 2 hours. The hearts were compared for indices of cell death, oxidative stress, and phase 2 enzyme activities. Hearts from the green tea group had a 65% to 85% decrease in markers of apoptosis, a tendency to higher total glutathione, and higher activities of the phase 2 enzymes glutamate cysteine ligase and quinone reductase. The results support a possible involvement of phase 2 enzymes in the protection by green tea catechins against myocardial IR injury.
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Affiliation(s)
- Masoumeh Akhlaghi
- School of Health and Nutrition, Shiraz University of Medical Sciences, Shiraz, Iran
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Peng PH, Chiou LF, Chao HM, Lin S, Chen CF, Liu JH, Ko ML. Effects of epigallocatechin-3-gallate on rat retinal ganglion cells after optic nerve axotomy. Exp Eye Res 2010; 90:528-34. [PMID: 20114044 DOI: 10.1016/j.exer.2010.01.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2009] [Revised: 12/22/2009] [Accepted: 01/20/2010] [Indexed: 11/28/2022]
Abstract
The purpose of this study was to investigate the effects of epigallocatechin-3-gallate (EGCG) in axotomized eyes and the pathways related to its action. Wistar rats received intracranial optic nerve (ON) axotomy 2 mm behind the globe in left eyes, whereas right eyes received sham operations. EGCG was administrated via intraperitoneal injection 30 min before and 4 days after axotomy. The density of retinal ganglion cell (RGC) was examined by a retrograde labeling technique. Western blot analysis was used to assess the expression of neuronal nitric oxide synthase (nNOS), Bax, Bcl-2, ERK and Akt. Optic nerve axotomy caused 54% RGC loss 7 days following surgery, and EGCG treatment reduced RGC loss by 12% (P = 0.017). The expression of the nNOS and pro-apoptotic Bax proteins were increased 5 days after axotomy, while EGCG treatment significantly blunted the up-regulation of the above two proteins (P = 0.04 and 0.02, respectively). Axotomy-induced p-ERK 1/2 and p-Akt proteins expression 5 days and 3 days following injury, respectively. Treatment with EGCG further enhanced p-ERK 1/2 and p-Akt expressions after axotomy. Inhibition of ERK and Akt pathways attenuated the protection of EGCG on RGC against axotomy damage. Thus, we demonstrated that administration of EGCG prior to axotomy promotes RGC survival. The neuroprotective capacity of EGCG appears to act through mediating nitric oxide, anti-apoptotic, and cell survival signaling pathways.
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Affiliation(s)
- Pai-Huei Peng
- Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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Kim H, Kawazoe T, Matsumura K, Suzuki S, Hyon SH. Long-Term Preservation of Rat Skin Tissue by Epigallocatechin-3-O-Gallate. Cell Transplant 2009; 18:513-9. [DOI: 10.1177/096368970901805-605] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Skin grafts can be preserved by cryopreservation and refrigerated storage at 4°C. Epigallocatechin-3- O-gallate (EGCG) enhances the viability of stored skin grafts and also extends the storage time up to 7 weeks at 4°C. EGCG, the major polyphenolic constituent present in green tea, has potent antioxidant, antimicrobial, antiproliferative, and free radical scavenging effects. This study examined the effects of EGCG on skin cryopreservation. Skin sample biopsy specimens from GFP rats were previously treated with/without EGCG then moved to −196°C. Skin samples were transplanted to nude mice after 2, 8, and 24 weeks of preservation. Glucose consumption was measured after thawing to assess the metabolic activity. Two weeks later the transplanted skin grafts were excised and histologically analyzed. Histological examinations revealed the degeneration of the epidermal and dermal layers in all groups. In the EGCG groups, the grafts showed higher integrity in the epidermal layer and dermal matrix. The present findings suggest the future clinical usefulness of EGCG for skin preservation; however, the mechanism by which EGCG promotes skin preservation still remains unclear.
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Affiliation(s)
- Hakhee Kim
- Department of Medical Simulation Engineering, Research Center for Nano Medical Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
| | - Takeshi Kawazoe
- Department of Plastic and Reconstructive Surgery, Kijunkai, Yoshikawa Hospital, Kyoto 606-8392, Japan
| | - Kazuaki Matsumura
- Department of Medical Simulation Engineering, Research Center for Nano Medical Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
| | - Shigehiko Suzuki
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
| | - Suong-Hyu Hyon
- Department of Medical Simulation Engineering, Research Center for Nano Medical Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
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