|
1
|
Savitikadi P, Dash L, Angadi KK, Reddy GB, Reddy VS. Systemically administered mini α-crystallin peptide delays cataract progression in streptozotocin-induced diabetic rats. Biochim Biophys Acta Gen Subj 2025; 1869:130814. [PMID: 40294808 DOI: 10.1016/j.bbagen.2025.130814] [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: 11/29/2024] [Revised: 04/21/2025] [Accepted: 04/24/2025] [Indexed: 04/30/2025]
Abstract
α-Crystallin in the mammalian eye lens composed of αA-Crystallin (αAC) and αB-Crystallin (αBC) subunits present in a 3:1 ratio. These proteins exhibit chaperone-like activity, helping to protect cells from various forms of stress. Specific sequences within αAC (70KFVIFLDVKHFSPEDLTVK88) and αBC (73DRFSVNLDVKHFSPEELKVK92) have been shown to possess effective chaperone and anti-apoptotic properties. However, their protective effects in diabetic cataract (DC) have not been explored. The current study explored the protective effects of systemically administered mini-αA and αBC peptides, both individually and in combination (3:1 ratio) against streptozotocin (STZ)-induced DC in rats. Hyperglycemia was induced in Sprague-Dawley rats through intraperitoneal (I.P.) injection of STZ, while control rats received PBS. Starting from the onset of cataract development, a group of diabetic rats was treated with mini-αA, or mini-αB, or their combination for four months via IP administration. Cataract progression and maturation were monitored using a slit lamp biomicroscope. To understand the underlying biochemical and molecular processes, we assessed changes in protein content, protein insolubilization, oxidative stress, endoplasmic reticulum (ER) stress, apoptotic cell death, and caspase-3 activity. Although the mini peptides did not prevent STZ-induced hyperglycemia, they delayed cataract progression in diabetic rats. Furthermore, mini peptides reduced protein aggregation and insolubilization, alleviated oxidative and ER stress, and mitigated hyperglycemia-induced apoptosis by lowering caspase-3 activity and Bax levels. This study demonstrates that systemic administration of mini α-crystallin peptides can delay DC progression by mitigating protein aggregation, oxidative stress, ER stress, and apoptosis. These findings suggest potential therapeutic applications for mini α-crystallin peptides in treating DC.
Collapse
Affiliation(s)
| | - Lucky Dash
- Biochemistry Division, ICMR-National Institute of Nutrition, Tarnaka, Hyderabad, India
| | - Kiran Kumar Angadi
- Biochemistry Division, ICMR-National Institute of Nutrition, Tarnaka, Hyderabad, India
| | - G Bhanuprakash Reddy
- Biochemistry Division, ICMR-National Institute of Nutrition, Tarnaka, Hyderabad, India
| | - V Sudhakar Reddy
- Biochemistry Division, ICMR-National Institute of Nutrition, Tarnaka, Hyderabad, India.
| |
Collapse
|
|
2
|
Buonfiglio F, Böhm EW, Tang Q, Daiber A, Gericke A. Revisiting the renin-angiotensin-aldosterone system in the eye: Mechanistic insights and pharmacological targets. Pharmacol Res 2025; 216:107771. [PMID: 40348100 DOI: 10.1016/j.phrs.2025.107771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 04/22/2025] [Accepted: 05/07/2025] [Indexed: 05/14/2025]
Abstract
The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in regulating blood pressure and fluid homeostasis through key effectors such as angiotensin II and aldosterone. These agents and their receptors have become crucial molecular targets in several cardiovascular and renal diseases. Over the past few decades, a growing body of evidence has revealed the presence of RAAS components in ocular structures, suggesting a tissue-specific RAAS within the eye. Building on this knowledge, studies have indicated that the ocular RAAS plays a significant role in the pathogenesis of various eye diseases. An impaired and overactivated RAAS contributes to the development of severe and widespread disorders affecting both the anterior and posterior segments of the eye. In this context, the current work aims to delve into the pivotal molecular pathways involving the RAAS, with an in-depth exploration of the ocular pathophysiology. It focuses on the relationship between overactivation of the RAAS and oxidative stress, as well as the exacerbation of neovascularization and inflammatory processes. The objective is to provide an updated and comprehensive understanding of the role of the RAAS in ophthalmological diseases, highlighting the therapeutic potential of RAAS modulators and discussing the controversies and challenges in this area of research.
Collapse
Affiliation(s)
- Francesco Buonfiglio
- Department of Ophthalmology, University Medical Center of the Johannes Gutenberg, University, Langenbeckstr.1, Mainz 55131, Germany.
| | - Elsa Wilma Böhm
- Department of Ophthalmology, University Medical Center of the Johannes Gutenberg, University, Langenbeckstr.1, Mainz 55131, Germany.
| | - Qi Tang
- Department of Ophthalmology, University Medical Center of the Johannes Gutenberg, University, Langenbeckstr.1, Mainz 55131, Germany.
| | - Andreas Daiber
- Department of Cardiology I, University Medical Center of the Johannes Gutenberg University, Mainz 55131, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz 55131, Germany.
| | - Adrian Gericke
- Department of Ophthalmology, University Medical Center of the Johannes Gutenberg, University, Langenbeckstr.1, Mainz 55131, Germany.
| |
Collapse
|
|
3
|
Li J, Buonfiglio F, Zeng Y, Pfeiffer N, Gericke A. Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon? Antioxidants (Basel) 2024; 13:1249. [PMID: 39456502 PMCID: PMC11505147 DOI: 10.3390/antiox13101249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/04/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Cataracts, a leading cause of blindness worldwide, are closely linked to oxidative stress-induced damage to lens epithelial cells (LECs). Key factors contributing to cataract formation include aging, arterial hypertension, and diabetes mellitus. Given the high global prevalence of cataracts, the burden of cataract-related visual impairment is substantial, highlighting the need for pharmacological strategies to supplement surgical interventions. Understanding the molecular pathways involved in oxidative stress during cataract development may offer valuable insights for designing novel therapeutic approaches. This review explores the role of oxidative stress in cataract formation, focusing on critical mechanisms, such as mitochondrial dysfunction, endoplasmic reticulum stress, loss of gap junctions, and various cell death pathways in LECs. Additionally, we discuss emerging therapeutic strategies and potential targeting options, including antioxidant-based treatments.
Collapse
Affiliation(s)
- Jingyan Li
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (F.B.); (Y.Z.); (N.P.)
| | | | | | | | - Adrian Gericke
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (F.B.); (Y.Z.); (N.P.)
| |
Collapse
|
|
4
|
Masuda F, Inami M, Takamura Y, Inatani M, Oki M. Identification of genes contributing to attenuation of rat model of galactose-induced cataract by pyruvate. Genes Cells 2024; 29:876-888. [PMID: 39219252 PMCID: PMC11555625 DOI: 10.1111/gtc.13150] [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: 05/24/2024] [Revised: 07/12/2024] [Accepted: 07/25/2024] [Indexed: 09/04/2024]
Abstract
Cataracts are a disease that reduces vision due to opacity formation of the lens. Diabetic cataracts occur at young age and progress relatively quickly, so the development of effective treatment has been awaited. Several studies have shown that pyruvate inhibits oxidative stress and glycation of lens proteins, which contribute to onset of diabetic cataracts. However, detailed molecular mechanisms have not been revealed. In this study, we attempted to reduce galactose-induced opacity by pyruvate with rat ex vivo model. Rat lenses were extracted and cultured in galactose-containing medium to induce lens opacity. After opacity had developed, continued culturing with pyruvate in the medium resulted in a reduction of lens opacity. Subsequently, we conducted microarray analysis to investigate the genes that contribute to the therapeutic effect. We performed quantitative expression measurements using RT-qPCR for extracted genes that were upregulated in cataract-induced lenses and downregulated in pyruvate-treated lenses, resulting in the identification of 34 candidate genes. Functional analysis using the STRING database suggests that metallothionein-related factors (Mt1a, Mt1m, and Mt2A) and epithelial-mesenchymal transition-related factors (Acta2, Anxa1, Cd81, Mki67, Timp1, and Tyms) contribute to the therapeutic effect of cataracts.
Collapse
Affiliation(s)
- Fuuga Masuda
- Department of Applied Chemistry and Biotechnology, Graduate School of EngineeringUniversity of FukuiFukuiJapan
| | - Mayumi Inami
- Technical Division, School of EngineeringUniversity of FukuiFukuiJapan
| | - Yoshihiro Takamura
- Department of Ophthalmology, Faculty of Medical SciencesUniversity of FukuiFukuiJapan
| | - Masaru Inatani
- Department of Ophthalmology, Faculty of Medical SciencesUniversity of FukuiFukuiJapan
| | - Masaya Oki
- Department of Applied Chemistry and Biotechnology, Graduate School of EngineeringUniversity of FukuiFukuiJapan
- Life Science Innovation CenterUniversity of FukuiFukuiJapan
| |
Collapse
|
|
5
|
Guo Z, Ma X, Zhang RX, Yan H. Oxidative stress, epigenetic regulation and pathological processes of lens epithelial cells underlying diabetic cataract. ADVANCES IN OPHTHALMOLOGY PRACTICE AND RESEARCH 2023; 3:180-186. [PMID: 38106550 PMCID: PMC10724013 DOI: 10.1016/j.aopr.2023.10.001] [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: 06/12/2023] [Revised: 09/11/2023] [Accepted: 10/04/2023] [Indexed: 12/19/2023]
Abstract
Background Cataract is a blinding disease worldwide. It is an age-related disease that mainly occurs in people over 65 years old. Cataract is also prevalent in patients with diabetes mellites (DM). The pathological mechanisms underlying diabetic cataract (DC) are more complex than that of age-related cataract. Studies have identified that polyol pathway, advanced glycation end products (AGEs) and oxidative stress are the primary pathogenesis of DC. In recent years, molecular-level regulations and pathological processes of lens epithelial cells (LECs) have been confirmed to play roles in the initiation and progression of DC. A comprehensive understanding and elucidation of how chronic hyperglycemia drives molecular-level regulations and cytopathological processes in the lens will shed lights on the prevention, delay and treatment of DC. Main text Excessive glucose in the lens enhances polyol pathway and AGEs formation. Polyol pathway causes imbalance in the ratio of NADPH/NADP+ and NADH/NAD+. Decrease in NADPH/NADP+ ratio compromises antioxidant enzymes, while increase in NADH/NAD+ ratio promotes reactive oxygen species (ROS) overproduction in mitochondria, resulting in oxidative stress. Oxidative stress in the lens causes oxidation of DNA, proteins and lipids, leading to abnormalities in their structure and functions. Glycation of proteins by AGEs decreases solubility of proteins. High glucose triggered epigenetic regulations directly or indirectly affect expressions of genes and proteins in LECs. Changes in autophagic activity, increases in fibrosis and apoptosis of LECs destroy the morphological structure and physiological functions of the lens epithelium, disrupting lens homeostasis. Conclusions In both diabetic animal models and diabetics, oxidative stress plays crucial roles in the formation of cataract. Epigenetic regulations, include lncRNA, circRNA, microRNA, methylation of RNA and DNA, histone acetylation and pathological processes, include autophagy, fibrosis and apoptosis of LECs also involved in DC.
Collapse
Affiliation(s)
- Zaoxia Guo
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, Xi'an, Shaanxi, China
| | - Xiaopan Ma
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, Xi'an, Shaanxi, China
| | - Rui Xue Zhang
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, China
| | - Hong Yan
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, Xi'an, Shaanxi, China
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, China
| |
Collapse
|
|
6
|
Nagaya M, Yamaoka R, Kanada F, Sawa T, Takashima M, Takamura Y, Inatani M, Oki M. Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract. PLoS One 2022; 17:e0273868. [PMID: 36417410 PMCID: PMC9683626 DOI: 10.1371/journal.pone.0273868] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 08/16/2022] [Indexed: 11/24/2022] Open
Abstract
Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to investigate the therapeutic effects of histone acetyltransferase (HAT) inhibitors. Among the tested HAT inhibitors, TH1834 was the only one that could reverse most of the opacity once it had formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. In lens cross-sections, vacuoles were present in the tissue of the cortical equatorial region of untreated cataract samples. In treated cataract samples, lens tissue regenerated to fill the vacuoles. To identify the genes regulated by HAT inhibitors, qRT-PCR was performed on treated and untreated cataract samples to determine candidate genes. Expression of Acta1 and Stmn4, both of which are involved in the cytoskeleton, were altered significantly in C646+CPTH2 samples. Expression of Emd, a nuclear membrane protein, and Prtfdc1, which is involved in cancer cell proliferation, were altered significantly in CBP30+CPTH2 samples. Acta1, Acta2, Arrdc3, Hebp2, Hist2h2ab, Pmf1, Ppdpf, Rbm3, RGD1561694, Slc16a6, Slfn13, Tagln, Tgfb1i1, and Tuba1c in TH1834 samples were significantly altered. These genes were primarily related to regulation of cell proliferation, the cytoskeleton, and cell differentiation. Expression levels increased with the onset of cataracts and was suppressed in samples treated with HAT inhibitors.
Collapse
Affiliation(s)
- Masaya Nagaya
- Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan
| | - Risa Yamaoka
- Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan
| | - Fumito Kanada
- Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan
| | - Tamotsu Sawa
- Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan
| | - Masaru Takashima
- Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan
| | - Yoshihiro Takamura
- Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masaru Inatani
- Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masaya Oki
- Department of Industrial Creation Engineering, Graduate School of Engineering, University of Fukui, Fukui, Japan
- Life Science Innovation Center, University of Fukui, Fukui, Japan
- * E-mail:
| |
Collapse
|
|
7
|
Amirahmadi M, Salesi M, Yousefi R, Daryanosh F, Nemati J, Kurganov BI. The impact of concurrent training and antioxidant supplementation on the factors associated with the ocular lens opacity in diabetic rats. Arch Physiol Biochem 2022; 128:126-140. [PMID: 31573372 DOI: 10.1080/13813455.2019.1668019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The current study was aimed to investigate the protective effect of vitamins C and E (VCE) supplementation, exercise, and their concurrent application against cataract incidence in the diabetic rats. The obtained results indicated that different supplementation and training treatments were capable to preserve the lens transparency in the diabetic rats. Also, upon applying different supplementation and training treatments, the level of glutathione (GSH) and activity of antioxidant enzymes in the diabetic rats was preserved approximately close to their control levels. In addition, different treatments were capable to maintain the structural integrity of the lens proteins in diabetic rats. Moreover, VCE supplementation, exercise and their simultaneous application prevented lens crystallins of diabetic rats against fibrillation and formation of the increased oligomeric sizes. The results of this study signify the importance of antioxidant supplementation and exercise in reducing the detrimental effects of hyperglycemia on the eye lenses.
Collapse
Affiliation(s)
- Mousa Amirahmadi
- Department of Sport Sciences, College of Education and Psychology, Shiraz University, Shiraz, Iran
| | - Mohsen Salesi
- Department of Sport Sciences, College of Education and Psychology, Shiraz University, Shiraz, Iran
| | - Reza Yousefi
- Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran
| | - Farhad Daryanosh
- Department of Sport Sciences, College of Education and Psychology, Shiraz University, Shiraz, Iran
| | - Javad Nemati
- Department of Sport Sciences, College of Education and Psychology, Shiraz University, Shiraz, Iran
| | - Boris I Kurganov
- Laboratory of Structural Biochemistry of Proteins, Bach Institute of Biochemistry, Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow, Russia
| |
Collapse
|
|
8
|
Liu Q, Wang X, Yan H. Effect of thioltransferase on oxidative stress induced by high glucose and advanced glycation end products in human lens epithelial cells. Int J Ophthalmol 2021; 14:965-972. [PMID: 34282379 DOI: 10.18240/ijo.2021.07.02] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 04/08/2021] [Indexed: 12/30/2022] Open
Abstract
AIM To study the effect of thioltransferase (TTase) on oxidative stress in human lens epithelial cells (HLECs) induced by high glucose and advanced glycation end products (AGEs). METHODS HLECs were treated with 35.5 mmol/L glucose or 1.5 mg/mL AGEs modified bovine serum albumin (AGEs-BSA) as the experimental groups, respectively. Cells were collected at the time point of 1, 2, 3, and 4d. The TTase activity were measured accordingly. TTase mRNA levels were detected by quantitative reverse transcription polymerase chain response (qRT-RCR) and its protein level was detected by Western blot. The siRNA was used to knock down the expression of TTase. The activity of catalase (CAT) and superoxide dismutase (SOD), the content of reactive oxygen species (ROS) and the ratio of oxidized glutathione/total glutathione (GSSG/T-GSH) were assessed in different groups, respectively. RESULTS The level of TTase mRNA gradually increased and reached the top at 2d, then it decreased to the normal level at 4d, and the TTase activity increased from 2 to 3d in both high glucose and AGEs-BSA groups. The TTase expression elevated from 2d in high glucose group, and it began to rise from 3d in AGEs-BSA group. The activity of CAT and SOD showed a decrease and the content of ROS and the ratio of GSSG/T-GSH showed an increase in high glucose and AGEs-BSA group. These biochemical alterations were more prominent in the groups with TTase siRNA. CONCLUSION High glucose and AGEs can increase ROS content in HLECs; therefore, it induces oxidative stress. This may result in the decreased GSH and increased GSSG content, impaired activity of SOD and CAT. The up-regulated TTase likely provides oxidation damage repair induced by high glucose and AGEs in the early stage.
Collapse
Affiliation(s)
- Qing Liu
- Xi'an People's Hospital (Xi'an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital School of Medicine, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.,Department of Ophthalmology, No.986 Hospital of Air Force, PLA, Air Force Medical University, Xi'an 710054, Shaanxi Province, China
| | - Xu Wang
- Department of Ophthalmology, Xi'an Hong Hui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Hong Yan
- Xi'an People's Hospital (Xi'an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital School of Medicine, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.,Department of Ophthalmology, Tangdu Hospital, Air Force Medical University, Xi'an 710038, Shaanxi Province, China
| |
Collapse
|
|
9
|
The Protective Effects of Flavonoids in Cataract Formation through the Activation of Nrf2 and the Inhibition of MMP-9. Nutrients 2020; 12:nu12123651. [PMID: 33261005 PMCID: PMC7759919 DOI: 10.3390/nu12123651] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 11/24/2020] [Accepted: 11/26/2020] [Indexed: 12/11/2022] Open
Abstract
Cataracts account for over half of global blindness. Cataracts formations occur mainly due to aging and to the direct insults of oxidative stress and inflammation to the eye lens. The nuclear factor-erythroid-2-related factor 2 (Nrf2), a transcriptional factor for cell cytoprotection, is known as the master regulator of redox homeostasis. Nrf2 regulates nearly 600 genes involved in cellular protection against contributing factors of oxidative stress, including aging, disease, and inflammation. Nrf2 was reported to disrupt the oxidative stress that activates Nuclear factor-κB (NFκB) and proinflammatory cytokines. One of these cytokines is matrix metalloproteinase 9 (MMP-9), which participates in the decomposition of lens epithelial cells (LECs) extracellular matrix and has been correlated with cataract development. Thus, during inflammatory processes, MMP production may be attenuated by the Nrf2 pathway or by the Nrf2 inhibition of NFκB pathway activation. Moreover, plant-based polyphenols have garnered attention due to their presumed safety and efficacy, nutritional, and antioxidant effects. Polyphenol compounds can activate Nrf2 and inhibit MMP-9. Therefore, this review focuses on discussing Nrf2's role in oxidative stress and cataract formation, epigenetic effect in Nrf2 activity, and the association between Nrf2 and MMP-9 in cataract development. Moreover, we describe the protective role of flavonoids in cataract formation, targeting Nrf2 activation and MMP-9 synthesis inhibition as potential molecular targets in preventing cataracts.
Collapse
|
|
10
|
Status of oxidative stress markers, advanced glycation index, and polyol pathway in age-related cataract subjects with and without diabetes. Exp Eye Res 2020; 200:108230. [DOI: 10.1016/j.exer.2020.108230] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/15/2020] [Accepted: 09/04/2020] [Indexed: 12/22/2022]
|
|
11
|
Song XL, Li MJ, Liu Q, Hu ZX, Xu ZY, Li JH, Zheng WL, Huang XM, Xiao F, Cui YH, Pan HW. Cyanidin-3- O-glucoside Protects Lens Epithelial Cells against High Glucose-Induced Apoptosis and Prevents Cataract Formation via Suppressing NF-κB Activation and Cox-2 Expression. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:8286-8294. [PMID: 32640796 DOI: 10.1021/acs.jafc.0c03194] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Diabetic cataract is one of the most important causes of blindness worldwide. Cyanidin-3-O-glucoside (C3G) is found to exert beneficial effects on many diabetic complications. However, its effect on diabetic cataract is not well known. Herein, we investigated the effect of C3G on high glucose-induced lens epithelial cell (SRA01/04) apoptosis and cataract formation as well as the involved mechanisms. We found C3G (20 μM) could preserve cell viability in SRA01/04 cells exposed to high glucose (100 μM). Meanwhile, C3G inhibited SRA01/04 cell apoptosis and regulated the Bcl-2/Bax ratio. Additionally, C3G suppressed NF-κB activation and subsequent cyclooxygenases-2 (Cox-2) expression, which are associated with the protection against apoptosis. Moreover, C3G attenuated lens opacity and protein aggregation in lens culture exposed to high glucose. In conclusion, C3G protected against high glucose-induced SRA01/04 cell apoptosis and cataract formation, which indicated the potential protection of anthocyanins on diabetic cataract.
Collapse
Affiliation(s)
- Xi-Ling Song
- Department of Public Health and Preventive Medicine, Jinan University, Guangzhou 510632, China
| | - Mei-Jun Li
- Department of Ophthalmology, the First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Qun Liu
- Department of Histology and Embryology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
| | - Zi-Xuan Hu
- Department of Public Health and Preventive Medicine, Jinan University, Guangzhou 510632, China
- West Campus, University of Chinese Acadamy of Sciences Shenzhen Hospital, Shenzhen 518107, China
| | - Zhi-Yi Xu
- Department of Ophthalmology, the First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Jia-Hui Li
- Department of Public Health and Preventive Medicine, Jinan University, Guangzhou 510632, China
| | - Wen-Lin Zheng
- Department of Public Health and Preventive Medicine, Jinan University, Guangzhou 510632, China
| | - Xiao-Mei Huang
- Department of Ophthalmology, the First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Fan Xiao
- Department of Public Health and Preventive Medicine, Jinan University, Guangzhou 510632, China
| | - Yu-Hong Cui
- Department of Histology and Embryology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
- Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 510260, China
| | - Hong-Wei Pan
- Department of Ophthalmology, the First Affiliated Hospital, Jinan University, Guangzhou 510632, China
- Institute of Ophthalmology, School of Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou 510632, China
| |
Collapse
|
|
12
|
Ślizień M, Bzoma B, Raczyńska D, Biedunkiewicz B, Śledziński Z, Dębska-Ślizień A, Glasner L. Ophthalmologic Diseases in Kidney Transplant Recipients: A Single-Center Prospective Study. Transplant Proc 2020; 52:2417-2422. [PMID: 32402454 DOI: 10.1016/j.transproceed.2020.02.098] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 02/05/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND Kidney transplant (KTx) recipients usually experience many comorbidities (eg, hypertension, diabetes, cardiovascular disease, glaucoma). They usually are older and have some ophthalmologic disorders, which may deteriorate after Ktx and some others may develop. OBJECTIVE We aimed to review a 1-year examination of the eyesight characteristics in patients after KTx. METHODS The study encompassed 82 eyes in 41 patients who underwent KTx in the years 2014 to 2018. All patients had visual acuity measurement, tonometry, slit lamp examination, and spectroscopic optical coherence tomography. RESULTS The most frequently observed changes during the 1-year observation were cataract (46%), hypertensive angiopathy (20%), and glaucoma (20%). One year after the renal transplant visual acuity declined in 22 patients (54%). In 45% of those with eyesight deterioration the cause was cataract, while in patients with no changes in eyesight (n = 9) cataract was not diagnosed. Patients with cataracts had been more often treated with high doses of steroids (steroid boluses), mainly because of acute rejection, which was significantly associated with cataract developing after Ktx (42% vs 11%; P = .019). On univariate analysis Charlson Comorbidity Index, total ischemic time, and steroid boluses were significantly associated with cataract developing after Ktx; none of these factors were an independent predictor on multivariate analysis. CONCLUSIONS The most common ophthalmologic diagnoses in patients after Ktx include cataract, glaucoma, and hypertensive angiopathy. Visual acuity deterioration, seen so often in the studied group of the patients, was mainly the effect of cataract progress. The effect of steroid boluses on cataract progress was meaningful.
Collapse
Affiliation(s)
- Mateusz Ślizień
- Department of Ophthalmology, Medical University of Gdańsk, Gdańsk, Poland.
| | - Beata Bzoma
- Department of Nephrology, Transplantology, and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Dorota Raczyńska
- Department of Ophthalmology, Medical University of Gdańsk, Gdańsk, Poland
| | - Bogdan Biedunkiewicz
- Department of Nephrology, Transplantology, and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Zbigniew Śledziński
- Department of General, Endocrinological, and Transplant Surgery, Medical University of Gdańsk, Gdańsk, Poland
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology, and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Leopold Glasner
- Department of Ophthalmology, Medical University of Gdańsk, Gdańsk, Poland
| |
Collapse
|
|
13
|
Turan G, Turan M. The Evaluation of TUNEL, PCNA and SOX2 Expressions in Lens Epithelial Cells of Cataract Patients with Pseudoexfoliation Syndrome. Curr Eye Res 2019; 45:12-16. [DOI: 10.1080/02713683.2019.1657463] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- Gulay Turan
- Faculty of Medicine, Department of Pathology, Balikesir University, Balikesir, Turkey
| | - Meydan Turan
- Department of Ophthalmology, Balikesir Ataturk City Hospital, Balikesir, Turkey
| |
Collapse
|
|
14
|
Investigation of expression and effects of TGF-β1 and MMP-9 in lens epithelial cells of diabetic cataract rats. Exp Ther Med 2019; 17:4522-4526. [PMID: 31086584 PMCID: PMC6488997 DOI: 10.3892/etm.2019.7471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 02/11/2019] [Indexed: 12/23/2022] Open
Abstract
Expressions and effects of transforming growth factor- 1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) in lens epithelial cells (LECs) of diabetic cataract rats were investigated. A total of 40 female Sprague-Dawley rats were randomly divided into study and control group. Rats in study group were successfully modeled diabetic cataract rats, and rats in control group were normal rats. Immunohistochemical staining was used to determine positive and negative granules in cytoplasm, and image proplus image analysis system to calculate the integral optical density of the average positive area. Quantitative analysis was performed on TGF-β1 and MMP-9 in LECs of rats in study and control groups at the 2nd and 4th weekends. There were no statistically significant differences in length and age between the two groups of rats (P>0.05). Glucose concentration in the blood of rats in study group after modeling was significantly higher than that before modeling (P<0.001), and that after modeling was significantly higher in study group than that in control group (P<0.001). The expression of TGF-β1 protein in LECs of rats in study group at T2 (the 4th weekend) was significantly higher than that at T1 (the 2nd weekend) (P<0.001), and that of TGF-β1 protein was significantly higher in study group than that in control group at T1 and T2 (P<0.001). The expression of MMP-9 protein in LECs of rats in study group at T2 was significantly higher than that at T1 (P<0.001), and that of MMP-9 protein was significantly higher in study group than that in control group at T1 and T2 (P<0.001). The TGF-β1 expression was positively correlated with the MMP-9 expression in LECs of diabetic cataract rats (r=0.825, P<001). The increased expression of MMP-9 and TGF-β1 may play an important role in the occurrence and development of diabetic cataract.
Collapse
|
|
15
|
Charakidas A, Kalogeraki A, Tsilimbaris M, Koukoulomatis P, Brouzas D, Delides G. Lens Epithelial Apoptosis and Cell Proliferation in Human Age-Related Cortical Cataract. Eur J Ophthalmol 2018; 15:213-20. [PMID: 15812762 DOI: 10.1177/112067210501500206] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Purpose To probe the presence of apoptosis in the epithelium of human lenses with age-related cortical cataract as well as to assess cell proliferation, a predicted consequence of apoptotic cell death, in this specific cell population. Methods DNA fragmentation was assessed using terminal digoxigenin-labeled dUTP nick end labeling (TUNEL) in capsulotomy specimens obtained from patients who underwent either extracapsular cataract extraction for the removal of adult-onset cortical cataract (n=27) or clear lens extraction for the correction of high myopia (n=25). Cell proliferation was assayed in 23 epithelia of cataractous lenses, and 20 epithelia of non-cataractous lenses with the proliferation marker MIB1, a monoclonal antibody against the nuclear antigen Ki-67 that is detected throughout the cell cycle but is absent in the resting (G0) cell. Results TUNEL staining was observed in 25 (92.6%) specimens of cataractous lenses, whereas cells undergoing apoptosis were identified in 2 (8%) of the epithelia from non-catarac-tous lenses. Only two MIB1-positive samples were detected, one of which was a capsule obtained during intracapsular cataract extraction. Conclusions The epithelium of human lenses with cortical cataract undergoes low rate apoptotic death. This limited epithelial apoptosis is unlikely to result in any significant cell density decrease since epithelial gaps are likely to be replaced by cell proliferation at the germinative zone of the anterior lens capsule. Nevertheless, the accumulation of small-scale epithelial losses during lifetime may induce alterations in lens fiber formation and homeostasis and result in loss of lens transparency.
Collapse
Affiliation(s)
- A Charakidas
- Department of Ophthalmology, Hippocration General Hospital, Athens, Greece.
| | | | | | | | | | | |
Collapse
|
|
16
|
Feng K, Guo HK. Eaf2 protects human lens epithelial cells against oxidative stress‑induced apoptosis by Wnt signaling. Mol Med Rep 2017; 17:2795-2802. [PMID: 29257273 PMCID: PMC5783493 DOI: 10.3892/mmr.2017.8246] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 04/24/2017] [Indexed: 01/11/2023] Open
Abstract
The tumor suppressor protein ELL-associated factor 2 (Eaf2) serves an important role in lens development and maturation; however, its role in oxidative stress-induced cataract formation remains unclear. In the present study, an in vitro apoptosis model was constructed by treating HLE-B3 cells with 50 µM hydrogen peroxide (H2O2), and was confirmed by flow cytometry. Subsequently, overexpression of Eaf2 was induced in H2O2-induced HLE-B3 cells by ligating Eaf2 cDNA to a pcDNA3.0 plasmid and the role of Wnt3a in the function of Eaf2 was also assessed by inhibiting the expression of the gene in Eaf2-overexpression cells. The expression levels of glycogen synthase kinase 3β, β-catenin, Eaf2, caspase 3, Wnt3a, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein were examined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Immunocytochemistry was used to locate Eaf2 and Wnt3 protein expression in the H2O2-induced HLE-B3 cells. The results indicated that Eaf2 was able to effectively suppress H2O2-induced apoptosis of HLE cells via inhibition of caspase 3 production and activation of Wnt3a signaling. In addition, knockdown of Wnt3a in Eaf2-overexpression cells evidently counteracted the effect of Eaf2 in antagonizing H2O2-induced apoptosis. Taken together, these findings suggested that Eaf2 may suppress oxidative stress-induced apoptosis of HLE-B3 cells exerted through the activation of Wnt3a signaling.
Collapse
Affiliation(s)
- Ke Feng
- Department of Ophthalmology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Hai-Ke Guo
- Department of Ophthalmology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| |
Collapse
|
|
17
|
Nagai N, Yamamoto T, Mitamura K, Taga A. Proteomic profile of the lens in a streptozotocin-induced diabetic rat model using shotgun proteomics. Biomed Rep 2017; 7:445-450. [PMID: 29181156 DOI: 10.3892/br.2017.988] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 09/14/2017] [Indexed: 01/09/2023] Open
Abstract
Streptozotocin (STZ)-induced diabetic rats (STZ rats) were used to investigate diabetic cataracts. In the current study, a shotgun liquid chromatography (LC)/mass spectrometry (MS)-based global proteomic analysis method was used to examine the mechanism of lens opacification as a result of hyperglycemia in STZ rats. The 6-week old Wistar rats were injected with STZ for 2 days (100 mg/kg/day, i.p.) and housed for 3 weeks. The plasma glucose levels were identified to be significantly higher when compared with the normal rats and insulin was not detected in the STZ rats. Furthermore, opacification of the cortical epithelium was observed in the lenses of STZ rats. A total of 235 proteins were identified in the lenses of the STZ rats and 229 in the lenses of the normal rats. A label-free semi-quantitative method, based on spectral counting, identified 52 proteins that were differentially expressed in the lenses of STZ rats compared with normal rats. In particular, superoxide dismutase, which is a critical antioxidant enzyme that detoxifies superoxide through redox cycling, was downregulated when analyzed by the semi-quantitative method. In addition, phosphorylated-p38, which is important in the signaling pathway involved in the oxidative stress response, was significantly increased in the lenses of STZ rats when compared with normal rats (P<0.05). Thus, the changes in protein expression were evaluated in the lenses of STZ rats using a shotgun LC/MS-based global proteomic analysis approach, and a decrease in antioxidant enzymes and an increase in oxidative stress were identified in the lenses of STZ rats. Further studies are required to examine the role of these proteins in the onset or progression of diabetic cataracts.
Collapse
Affiliation(s)
- Noriaki Nagai
- Department of Advanced Design for Pharmaceuticals, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka 577-8502, Japan
| | - Tetsushi Yamamoto
- Pathological and Biomolecule Analyses Laboratory, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka 577-8502, Japan
| | - Kuniko Mitamura
- Pathological and Biomolecule Analyses Laboratory, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka 577-8502, Japan
| | - Atsushi Taga
- Pathological and Biomolecule Analyses Laboratory, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka 577-8502, Japan
| |
Collapse
|
|
18
|
López-Valverde G, Garcia-Martin E, Fernández-Mateos J, Cruz-González F, Larrosa-Povés JM, Polo-Llorens V, Pablo-Júlvez LE. Asociación de factores de riesgo ambientales en el desarrollo de las cataratas preseniles. REVISTA MEXICANA DE OFTALMOLOGÍA 2017. [DOI: 10.1016/j.mexoft.2016.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
|
|
19
|
Kaur A, Gupta V, Christopher AF, Malik MA, Bansal P. Nutraceuticals in prevention of cataract - An evidence based approach. Saudi J Ophthalmol 2017; 31:30-37. [PMID: 28337060 PMCID: PMC5352946 DOI: 10.1016/j.sjopt.2016.12.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 11/02/2016] [Accepted: 12/06/2016] [Indexed: 11/01/2022] Open
Abstract
Cataract is a principal cause of blindness in the world and is characterized by clouding of eye's natural lens. Surgery is the major therapeutic step taken to cure cataract; however, it is having its own limitations and complications such as iris prolapse, raised IOP, infection, cystoid macular edema and posterior capsular opacification (PCO). So world is looking toward more robust and natural ways to prevent cataract. One of the important factors that can play a role in prevention of any and many diseases is diet of the people. The inclusion of certain naturally occurring food and nutraceuticals is coming up as a best alternative for curing cataract because of their presumed safety, potential nutritional and therapeutic effects. Some nutraceuticals can act as an anticataract agent through some or the other molecular mechanism if consumed by normal population deliberately or inadvertently.
Collapse
Affiliation(s)
- Amandeep Kaur
- University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, Punjab, India
| | - Vikas Gupta
- University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, Punjab, India
| | - Ajay Francis Christopher
- University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, Punjab, India
| | - Manzoor Ahmad Malik
- Cancer Diagnostic and Research Centre, Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir 190011, India
| | - Parveen Bansal
- University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, Punjab, India
| |
Collapse
|
|
20
|
Osnes-Ringen Ø, Berg KH, Moe MC, Zetterström C, Røger M, Nicolaissen B. Cell death pattern in lens epithelium of cataract patients. Acta Ophthalmol 2016; 94:514-20. [PMID: 27061232 DOI: 10.1111/aos.13009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 01/09/2016] [Indexed: 11/26/2022]
Abstract
PURPOSE Apoptosis, a type of programmed cell death, is observed in various types of cataract and in cultured lens epithelium subjected to oxidative damage. We have recently described oxidative DNA base damage in epithelium in age-related cataract and cultured cells, and we here aimed to examine such epithelium for markers for proliferation, initiation of apoptosis and morphological patterns of cell damage. METHODS Samples (n = 75) were analysed by light microscopy/electron microscopy (LM/EM); immunohistochemistry (IHC) for PCNA and Ki67 (DNA synthesis/proliferation); TUNEL assay (DNA fragmentation/apoptosis); and protein/gene expression of Caspase-3 (apoptotic effector molecule) and BAX/Bcl2 (pro-/anti-apoptotic marker) in fresh/cultured epithelium by IHC and qRT-PCR. RESULTS In fresh samples, the majority of cells were Ki67-/PCNA+. BAX/BCL-2-ratio was approximately 1, and Caspase-3 levels were low. TUNEL stained scattered nuclei/nuclear fragments (9/6302 cells). Main morphological signs of cell damage included rupture of cell membranes and hydration of cytoplasm and nuclei. Cultivation increased levels of BAX and Bcl2 by IHC and qRT-PCR (approximately 10-fold upregulation). Caspase-3 levels remained low by IHC with similar expression in fresh and cultured samples by qRT-PCR. CONCLUSION Genomic stress and DNA repair may explain the contrasting expression of Ki67/PCNA in fresh epithelium. Despite low levels of Caspase-3 and similar expression of BAX/Bcl-2, a low incidence of apoptosis may be detected in epithelium in age-related corticonuclear cataract. Epithelium may be transferred to culture without an increase in expression of Caspase-3, one of the central mediators of apoptosis.
Collapse
Affiliation(s)
- Øyvind Osnes-Ringen
- Center for Eye Research; Department of Ophthalmology; Oslo University Hospital; University of Oslo; Oslo Norway
| | - Kristiane Haug Berg
- Center for Eye Research; Department of Ophthalmology; Oslo University Hospital; University of Oslo; Oslo Norway
| | - Morten C. Moe
- Center for Eye Research; Department of Ophthalmology; Oslo University Hospital; University of Oslo; Oslo Norway
| | - Charlotta Zetterström
- Center for Eye Research; Department of Ophthalmology; Oslo University Hospital; University of Oslo; Oslo Norway
| | - Magnus Røger
- Department of Pathology; Oslo University Hospital; Oslo Norway
| | - Bjørn Nicolaissen
- Center for Eye Research; Department of Ophthalmology; Oslo University Hospital; University of Oslo; Oslo Norway
| |
Collapse
|
|
21
|
Li D, Qiu X, Yang J, Liu T, Luo Y, Lu Y. Generation of Human Lens Epithelial-Like Cells From Patient-Specific Induced Pluripotent Stem Cells. J Cell Physiol 2016; 231:2555-62. [PMID: 26991066 DOI: 10.1002/jcp.25374] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 03/11/2016] [Indexed: 12/17/2022]
Affiliation(s)
- Dan Li
- Research Center; Eye & ENT Hospital of Fudan University; Shanghai China
- Key Laboratory of Myopia; Ministry of Health; Shanghai China
- State Key Laboratory of Molecular Engineering of Polymers; Fudan University; Shanghai China
| | - Xiaodi Qiu
- Key Laboratory of Myopia; Ministry of Health; Shanghai China
- Department of Ophthalmology; Eye & ENT Hospital of Fudan University; Shanghai China
| | - Jin Yang
- Key Laboratory of Myopia; Ministry of Health; Shanghai China
- Department of Ophthalmology; Eye & ENT Hospital of Fudan University; Shanghai China
| | - Tianjin Liu
- Institute of Biochemistry and Cell Biology; Shanghai Institutes for Biological Sciences; Chinese Academy for Sciences; Shanghai China
| | - Yi Luo
- Key Laboratory of Myopia; Ministry of Health; Shanghai China
- Department of Ophthalmology; Eye & ENT Hospital of Fudan University; Shanghai China
| | - Yi Lu
- Key Laboratory of Myopia; Ministry of Health; Shanghai China
- Department of Ophthalmology; Eye & ENT Hospital of Fudan University; Shanghai China
| |
Collapse
|
|
22
|
Ahn YJ, Kim MS, Chung SK. Calpain and Caspase-12 Expression in Lens Epithelial Cells of Diabetic Cataracts. Am J Ophthalmol 2016; 167:31-7. [PMID: 27130368 DOI: 10.1016/j.ajo.2016.04.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 04/12/2016] [Accepted: 04/13/2016] [Indexed: 11/28/2022]
Abstract
PURPOSE To compare the expression of calpain and caspase-12 in human lens epithelial cells (LECs) of cataract patients with or without diabetic retinopathy (DR). DESIGN Prospective, comparative case series. METHODS Patients were divided into 4 groups: patients without diabetes mellitus (DM) (Group 1), patients with DM and without diabetic retinopathy (DR) (Group 2), diabetic patients with nonprolifeative DR (NPDR) (Group 3), and diabetic patients with proliferative DR (PDR) (Group 4). Data on DM duration and glycated hemoglobin (HbA1c) level were collected. The LECs were obtained during cataract surgery and immunohistochemical staining was performed for calpain and caspase-12. The reactivity score of each specimen was determined using confocal microscopy. RESULTS A total of 40 patients (40 eyes) were evaluated, and each group was composed of 10 patients. The expression of calpain and caspase-12 was highest in Group 4, followed by Group 3, Group 2, and Group 1 (P < .001). The expressions were significantly higher with a longer duration of DM, increased HbA1c level, or advanced DR. CONCLUSIONS Endoplasmic reticulum stress may be associated with apoptosis of LECs, resulting in cataract formation in diabetic patients.
Collapse
Affiliation(s)
- Ye Jin Ahn
- Department of Ophthalmology and Visual Science, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Man Soo Kim
- Department of Ophthalmology and Visual Science, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sung Kun Chung
- Department of Ophthalmology & Visual Science, St Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
| |
Collapse
|
|
23
|
Dai J, Liu H, Zhou J, Huang K. Selenoprotein R Protects Human Lens Epithelial Cells against D-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress. Int J Mol Sci 2016; 17:231. [PMID: 26875981 PMCID: PMC4783963 DOI: 10.3390/ijms17020231] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 01/31/2016] [Accepted: 02/04/2016] [Indexed: 11/17/2022] Open
Abstract
Selenium is an essential micronutrient for humans. Much of selenium's beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on d-galactose-induced apoptosis in hLE cells were studied. The results showed that both d-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to d-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by d-galactose, implying that selenium as a micronutrient may play important roles in hLE cells.
Collapse
Affiliation(s)
- Jie Dai
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Hongshan, Wuhan 430074, China.
| | - Hongmei Liu
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Hongshan, Wuhan 430074, China.
| | - Jun Zhou
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Hongshan, Wuhan 430074, China.
| | - Kaixun Huang
- Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Hongshan, Wuhan 430074, China.
| |
Collapse
|
|
24
|
Knockdown of 15-kDa selenoprotein (Sep15) increases hLE cells' susceptibility to tunicamycin-induced apoptosis. J Biol Inorg Chem 2015; 20:1307-17. [PMID: 26531105 DOI: 10.1007/s00775-015-1309-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 10/21/2015] [Indexed: 10/22/2022]
Abstract
In this work, we investigated the effect of Sep15 gene knockdown on apoptosis in human lens epithelial (hLE) cells, trying to understand the relevance of Sep15 to cataract formation in the Sep15 knockout (KO) mice. The results showed that sole knockdown of Sep15 by RNA interference did not result in apoptosis; however, reduction of Sep15 expression aggravated tunicamycin (Tm)-induced cell apoptosis and caspases activation. Furthermore, Tm-induced mitochondrial dysfunction was also exacerbated under the Sep15 knockdown condition by measurement of mitochondrial membrane potential decrease and human cytochrome c release into cytosol. Interestingly, the knockdown of Sep15 exacerbated Tm-induced oxidative stress while endoplasmic reticulum (ER) stress was not correspondingly elevated. These results suggest that the protective role of Sep15 against Tm-induced apoptosis in hLE cells is operated via inhibiting oxidative stress rather than regulating Tm-induced ER stress, and the protective role becomes dependent on Sep15 only in acute stress condition.
Collapse
|
|
25
|
Fang H, Hu X, Wang M, Wan W, Yang Q, Sun X, Gu Q, Gao X, Wang Z, Gu L, Oliver Chen CY, Wei X. Anti-osmotic and antioxidant activities of gigantol from Dendrobium aurantiacum var. denneanum against cataractogenesis in galactosemic rats. JOURNAL OF ETHNOPHARMACOLOGY 2015; 172:238-246. [PMID: 26119284 DOI: 10.1016/j.jep.2015.06.034] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 05/07/2015] [Accepted: 06/11/2015] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Dendrobium aurantiacum var. denneanumis widespread in southern China, locally known as "Shihu", "Huangcao" or "Fengdou", has long been used in traditional Chinese medicine for antipyretic, immunomodulatory, anti-aging effects and eye benefiting. AIM OF THIS STUDY To investigate the effects of gigantol extracted from the stem of D. aurantiacum var. denneanum on the formation of galactose-induced cataractogenesis and the potential mechanisms underlying these effects. MATERIALS AND METHODS Cataract lens models were induced by d-galactose both in vitro and in vivo. The transparency of the rat lenses in vitro and in vivo was observed with an anatomical microscope and a slit lamp microscope. The differential protein and action targets of gigantol were determined and compared among the control group, model group, and gigantol group using two-dimensional electrophoresis and mass spectrometry (MS). Enzyme kinetics was used to show the ability of gigantol to respress aldose reductase (AR) and inducible nitric oxide synthase (iNOS). Quantitative real-time PCR (RT-qPCR). was used to detect repression of the expression of AR and iNOS genes. Molecular docking and dynamic simulation were used to predict the interaction points and combination patterns between gigantol, AR, and iNOS. RESULTS Gigantol was found to prevent galactose-induced damage to the rat lenses both in vitro and in vivo, to delay lens turbidity, and to keep the lenses transparent. Differential proteomes, MS, and RT-qPCR showed AR and iNOS to be the target proteins of gigantol. Gigantol reduced the galactose-induced AR and iNOS mRNA expression by 51.2% and 60.9%, respectively. The IC50 of gigantol for inhibition of AR and iNOS activities were 65.67 μg/mL and 8.768 μg/mL, respectively. Gigantol-AR binding sites were Trp111, His110, Tyr48, and Trp20, and gigantol-iNOS binding sites were Ile195 and Gln257. The main forms of interaction were hydrophobic forces, hydrogen bonds, and van der Waals forces. CONCLUSION Gigantol extracted from D. aurantiacum var. denneanum was found to inhibit galactose-induced formation of cataracts through repression of the gene expression and activity of AR and iNOS.
Collapse
Affiliation(s)
- Hua Fang
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Xiaohong Hu
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Meiling Wang
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Wencheng Wan
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Qiaohong Yang
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Xiaosheng Sun
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Qiong Gu
- Institute of Drug Synthesis and Pharmaceutical Processing, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, PR China
| | - Xinxin Gao
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Zhengtao Wang
- Shanghai R&D Center for Standardization of Chinese Medicines, Institute of Chinese Materia Medica of Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China
| | - Lianquan Gu
- Institute of Drug Synthesis and Pharmaceutical Processing, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, PR China
| | - C-Y Oliver Chen
- Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
| | - Xiaoyong Wei
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
| |
Collapse
|
|
26
|
Cytomorphometric study of epithelial cells in normal and cataractous human lenses in relation with hyperglycemia. Int Ophthalmol 2015; 36:147-58. [PMID: 26073139 DOI: 10.1007/s10792-015-0082-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Accepted: 05/06/2015] [Indexed: 10/23/2022]
Abstract
The aim of the study is to evaluate and correlate the morphology and cell density of epithelial cells adhering to lens capsule surgically removed from the anterior central region with lens clarity and type of cataract present in patients with or without type 2 diabetes. Capsulorhexis specimens were obtained from patients who had undergone phacoemulsification cataract surgery. All the samples were centrifuged and stained by the aid of Papanicolaou technique and were observed under light microscope. We determinated the mean cell density, the degree of epithelial damage, and morphological indicators of cells such as cell area and the nucleus-plasma ratio. Patients with cataract demonstrated a statistical significant decrease in cell density and an heterogeneous cell picture in which enlarged cells dominated. In addition, type 2 diabetics with cataract had a significantly even lower mean epithelial cell density by the presence of larger cell area with smaller nucleus-plasma ratio. More pronounced alterations in the lens epithelium were correlated not only with the presence of cortical cataract, increased fasting blood sugar, and increased HbA1c but also with the prolonged duration of diabetes and the co-existence of diabetic retinopathy. It seems that density and morphology of the anterior lens epithelial cells determine the lens epithelium damage which is more profound in hyperglycemia and in cortical cataracts. The changes in lens epithelium seem to play an important role in cataractogenesis.
Collapse
|
|
27
|
Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes 2015; 6:92-108. [PMID: 25685281 PMCID: PMC4317321 DOI: 10.4239/wjd.v6.i1.92] [Citation(s) in RCA: 180] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 11/22/2014] [Accepted: 12/03/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world's most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.
Collapse
|
|
28
|
Lim SA, Joo CK, Kim MS, Chung SK. Expression of p53 and caspase-8 in lens epithelial cells of diabetic cataract. J Cataract Refract Surg 2014; 40:1102-8. [PMID: 24957431 DOI: 10.1016/j.jcrs.2013.12.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/28/2013] [Accepted: 12/17/2013] [Indexed: 11/27/2022]
Abstract
PURPOSE To determine expression of apoptotic factors p53 and caspase-8 in human lens epithelial cells (LECs) of cataract patients with or without diabetic retinopathy (DR), the duration of diabetes mellitus (DM), and the level of glycated hemoglobin (hemoglobin A1c [HbA1c]). SETTING St. Mary's Hospital, Catholic University of Korea, Seoul, South Korea. DESIGN Randomized prospective study. METHODS The LECs were isolated during cataract surgery. The isolated samples were classified into 4 groups as follows: patients without DM (Group 1), patients with DM but not DR (Group 2), diabetic patients with nonproliferative DR (Group 3), and diabetic patients with proliferative DR (Group 4). To explore the mechanism of apoptosis, the expressions of p53 and caspase-8 were measured by immunohistochemical staining and compared with the data according to the duration of DM, HbA1c levels, and severity of DR. RESULTS All groups comprised 15 eyes. The expressions of P53 and caspase-8 were higher in Groups 2, 3, and 4 than in Group 1 (P<.001). The expressions were statistically significantly increased with a longer duration of DM, higher HbA1c levels, and advanced DR. CONCLUSIONS The expressions of P53 and caspase-8 were strong in patients with DM and advanced DR. Knowledge of these relationships may lead to a better understanding of the development of diabetic cataract. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned.
Collapse
Affiliation(s)
- Sung A Lim
- From the Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital (Lim, Joo, Kim), and St. Paul's Hospital (Chung), College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea
| | - Choun-Ki Joo
- From the Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital (Lim, Joo, Kim), and St. Paul's Hospital (Chung), College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea
| | - Man Soo Kim
- From the Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital (Lim, Joo, Kim), and St. Paul's Hospital (Chung), College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea
| | - Sung Kun Chung
- From the Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital (Lim, Joo, Kim), and St. Paul's Hospital (Chung), College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea.
| |
Collapse
|
|
29
|
Manaviat MR, Oveisi N, Zare-Bidoki A. Accelerated bilateral cataract formation as a first manifestation of diabetes mellitus. Prague Med Rep 2014; 114:258-62. [PMID: 24485343 DOI: 10.14712/23362936.2014.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
There is a proved relationship between diabetes mellitus and the cataract formation. The incidence of this is usually related to the duration of diabetes. In this manuscript we report a 15 years old female presented to the emergency room with a 4 hour history of rapid bilateral diminished vision, initially diagnosed with idiopathic cataracts, but after more laboratory evaluations revealed new-onset type 1 diabetes mellitus without ketosis.
Collapse
Affiliation(s)
- M R Manaviat
- Department of Ophthalmology, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - N Oveisi
- Department of Ophthalmology, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - A Zare-Bidoki
- Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| |
Collapse
|
|
30
|
Kim B, Kim SY, Chung SK. Changes in apoptosis factors in lens epithelial cells of cataract patients with diabetes mellitus. J Cataract Refract Surg 2012; 38:1376-81. [PMID: 22727992 DOI: 10.1016/j.jcrs.2012.04.026] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2012] [Revised: 03/30/2012] [Accepted: 04/02/2012] [Indexed: 11/29/2022]
Abstract
PURPOSE To determine and compare the expression of apoptotic factors Bax and Bcl-2 in lens epithelial cells (LECs) of cataract patients with and without diabetic retinopathy (DR), the duration of diabetes mellitus (DM), and the glycated hemoglobin (HbA1c) level. SETTING St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. DESIGN Randomized prospective study. METHODS Patients were classified into 3 groups as follows: patients without DM (Group 1), patients with DM but without DR (Group 2), and diabetic patients with DR (Group 3). Data on the duration of DM and the HbA1c levels were recorded. The anterior capsule was obtained from the patients after cataract surgery, and immunohistochemical stains of Bax and Bcl-2 were performed. The stained anterior capsules were analyzed by reactivity scoring. RESULTS Each group comprised 20 eyes. There was a statistically significant increase in Bax expression in all groups (P<.001). The Bcl-2 expression increased more in Group 2 and Group 3 than in Group 1, although the difference was not significant (P=.615). With a longer duration of DM and higher HbA1c level, Bax expression significantly increased but Bcl-2 was weakly expressed. CONCLUSIONS The apoptosis in LECs increased in cataract patients with DM and with or without DR. Using this knowledge on the regulation of apoptosis will permit better identification of the factors involved in the etiology of diabetes and may result in new therapies for diabetic cataract. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned.
Collapse
Affiliation(s)
- Boyun Kim
- Department of Ophthalmology, St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea
| | | | | |
Collapse
|
|
31
|
Suresha BS, Sattur AP, Srinivasan K. Beneficial influence of fungal metabolite nigerloxin on eye lens abnormalities in experimental diabetes. Can J Physiol Pharmacol 2012; 90:387-94. [DOI: 10.1139/y11-135] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Osmotic and oxidative stress have been implicated in the pathogenesis of diabetic cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibitory and free radical scavenging potential, in vitro. In the present study, the beneficial influence of nigerloxin was investigated on diabetes-induced alteration in the eye lens of rats treated with streptozotocin. Groups of diabetic rats were administered nigerloxin orally (100 mg·(kg body mass)–1·day–1) for 30 days. The activity of lens polyol pathway enzymes (aldose reductase and sorbitol dehydrogenase), lipid peroxides, and advanced glycation end products (AGEs) were increased in the diabetic animals. Levels of glutathione as well as the activity of antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase) were decreased in the eye lens of the diabetic animals. The administration of nigerloxin significantly decreased levels of lipid peroxides and AGEs in the lens of the diabetic rats. Increase in the activity of aldose reductase and sorbitol dehydrogenase in the lens was countered by nigerloxin treatment. The activity of glutathione and antioxidant enzyme in the lens was significantly elevated in nigerloxin-treated diabetic rats. Examination of the treated rats’ eyes indicated that nigerloxin delayed cataractogenesis in the diabetic rats. The results suggest the beneficial countering of polyol pathway enzymes and potentiation of the antioxidant defense system by nigerloxin in diabetic animals, implicating its potential in ameliorating cataracts in diabetics.
Collapse
Affiliation(s)
- Bharathinagar S. Suresha
- Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CFTRI), Council of Scientific and Industrial Research (CSIR), Mysore 570 020, Karnataka, India
| | - Avinash P. Sattur
- Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CFTRI), Council of Scientific and Industrial Research (CSIR), Mysore 570 020, Karnataka, India
| | - Krishnapura Srinivasan
- Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CFTRI), Council of Scientific and Industrial Research (CSIR), Mysore 570 020, Karnataka, India
| |
Collapse
|
|
32
|
Ou Y, Liao G, Yuan Z, Wu W. Protective Effect of Recombinant Hirudin Variant III against Galactose-Mediated Rat Lens Epithelial Cell Damage. Curr Eye Res 2012; 37:187-94. [DOI: 10.3109/02713683.2011.643269] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
33
|
Kim YS, Kim NH, Lee YM, Kim JS. Preventive Effect of Chlorogenic Acid on Lens Opacity and Cytotoxicity in Human Lens Epithelial Cells. Biol Pharm Bull 2011; 34:925-8. [DOI: 10.1248/bpb.34.925] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Young Sook Kim
- Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM)
| | - Nan Hee Kim
- Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM)
| | - Yun Mi Lee
- Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM)
| | - Jin Sook Kim
- Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM)
| |
Collapse
|
|
34
|
Diabetic cataract-pathogenesis, epidemiology and treatment. J Ophthalmol 2010; 2010:608751. [PMID: 20634936 PMCID: PMC2903955 DOI: 10.1155/2010/608751] [Citation(s) in RCA: 240] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2009] [Accepted: 04/02/2010] [Indexed: 12/15/2022] Open
Abstract
Cataract in diabetic patients is a major cause of blindness in developed and developing countries. The pathogenesis of diabetic cataract development is still not fully understood. Recent basic research studies have emphasized the role of the polyol pathway in the initiation of the disease process.
Population-based studies have greatly increased our knowledge concerning the association between diabetes and cataract formation and have defined risk factors for the development of cataract. Diabetic patients also have a higher risk of complications after phacoemulsification cataract surgery compared to nondiabetics. Aldose-reductase inhibitors and antioxidants have been proven beneficial in the prevention or treatment of this sightthreatening condition in in vitro and in vivo experimental studies.
This paper provides an overview of the pathogenesis of diabetic cataract, clinical studies investigating the association between diabetes and cataract development, and current treatment of cataract in diabetics.
Collapse
|
|
35
|
Khalfaoui T, Basora N, Ouertani-Meddeb A. Apoptotic factors (Bcl-2 and Bax) and diabetic retinopathy in type 2 diabetes. J Mol Histol 2010; 41:143-52. [DOI: 10.1007/s10735-010-9271-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2010] [Accepted: 05/25/2010] [Indexed: 12/11/2022]
|
|
36
|
Ajani EO, Salako AA, Sharlie PD, Akinleye WA, Adeoye AO, Salau BA, Adebawo OO. Chemopreventive and remediation effect of Hydrocotyl bonariensis Comm. Ex Lam (Apiaceae) leave extract in galactose-induced cataract. JOURNAL OF ETHNOPHARMACOLOGY 2009; 123:134-142. [PMID: 19429352 DOI: 10.1016/j.jep.2009.02.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2008] [Revised: 01/06/2009] [Accepted: 02/02/2009] [Indexed: 05/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hydrocotyl bonariensis Comm. Ex Lam (Apiaceae) is being widely used in Western Nigeria in treating various symptoms of ophthalmic diseases; however scientific data in support of this medicinal use have not been reported. AIM OF THE STUDY This study, investigated the efficacy of Hydrocotyl bonariensis leave extract in offering protection against experimental cataract and also examined its remediation effect when administered after cataract onset. MATERIALS AND METHODS Weanling albino rats fed with 30% galactose diet were used in the study. Mechanisms of action of the extract were investigated by measuring the degree of lens peroxidation, lens antioxidant status and lens protein concentration. Severity of cataract was determined by measuring the cataract index. RESULTS The extract at 500 mg kg(-1) reduced cataract index significantly and also reduced cataract progression when administered after cataract onset. Administration of this dosage also significantly reduced the degree of lens peroxidation, increased the level of reduced glutathione (GSH) and the lens catalase and superoxide dismutase activity. The extract also prevents protein insolubilization. Administration of the extract at 1000 mg kg(-1) reduced cataract index and lens peroxidation but did not increase the antioxidant status significantly. Administration of the extract after cataract onset reduced cataract index, moderately increased percentage soluble protein above the value prior to the arrest of hypergalactosemia but did not increase the antioxidant status. CONCLUSION Our study suggests that Hydrocotyl bonariensis protects against galactose-induced cataract, and that administration of the extract after cataract onset reduced cataract progression but did not reverse cataractogenesis.
Collapse
Affiliation(s)
- E O Ajani
- Department of Biochemistry, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, P. M. B. 2005, Ago-Iwoye, Nigeria.
| | | | | | | | | | | | | |
Collapse
|
|
37
|
Ou Y, Geng P, Liao GY, Zhou Z, Wu WT. Intracellular GSH and ROS levels may be related to galactose-mediated human lens epithelial cell apoptosis: Role of recombinant hirudin variant III. Chem Biol Interact 2009; 179:103-9. [DOI: 10.1016/j.cbi.2008.10.039] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2008] [Revised: 10/09/2008] [Accepted: 10/09/2008] [Indexed: 10/21/2022]
|
|
38
|
Abstract
The ocular lens is a distinct system to study cell death for the following reasons. First, during animal development, the ocular lens is crafted into its unique shape. The crafting processes include cell proliferation, cell migration, and apoptosis. Moreover, the lens epithelial cells differentiate into lens fiber cells through a process, which utilizes the same regulators as those in apoptosis at multiple signaling steps. In addition, introduction of exogenous wild-type or mutant genes or knock-out of the endogenous genes leads to apoptosis of the lens epithelial cells followed by absence of the ocular lens or formation of abnormal lens. Finally, both in vitro and in vivo studies have shown that treatment of adult lens with stress factors induces apoptosis of lens epithelial cells, which is followed by cataractogenesis. The present review summarizes the current knowledge on apoptosis in the ocular lens with emphasis on its role in lens development and pathology.
Collapse
Affiliation(s)
- Qin Yan
- College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China
| | | | | |
Collapse
|
|
39
|
Abstract
Studies have been conducted to ascertain the preventive effect of pyruvate against diabetes induced damage to DNA and associated morphogenetic changes in the mouse lens. Such changes were characterized by DNA nicks as well as by gross morphological changes in the nuclei, evident respectively by TUNEL and Hoechst staining procedures. Morphogenetic changes were also apparent by abnormal diferentiation of the germinal epithelial cells and errors in their migratory pathway. These changes were prevented by simultaneous administration of pyruvate to the diabetic animals. The preventive effect of this agent is attributable to its property of scavenging oxy-radicals generated by high levels of the sugars.
Collapse
Affiliation(s)
- K R Hegde
- Department of Ophthalmology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | | |
Collapse
|
|
40
|
Kubo E, Urakami T, Fatma N, Akagi Y, Singh DP. Polyol pathway-dependent osmotic and oxidative stresses in aldose reductase-mediated apoptosis in human lens epithelial cells: role of AOP2. Biochem Biophys Res Commun 2004; 314:1050-6. [PMID: 14751239 DOI: 10.1016/j.bbrc.2004.01.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Aldose reductase (AR) has been implicated as a major contributor to the pathogenesis of diabetic cataracts. AR activation generates osmotic and oxidative stresses via the polyol pathway and induces cell death signals. Antioxidant protein 2 (AOP2) protects cells from oxidative stress. We investigated the effect of AR overexpression on polyol accumulation and on hyperglycemic oxidative stress and osmotic stress, as well as the effects of these stresses on human lens epithelial cell (hLEC) survival. hLECs overexpressing the AR became apoptotic during hyperglycemia and showed elevated levels of intracellular polyols. Glutathione and AOP2 levels were significantly decreased in these cells. Interestingly, supply of AOP2 and/or the AR inhibitor fidarestat protected the cells against hyperglycemia-induced death. Overexpression of AR increased osmotic and oxidative stresses, resulting in increased apoptosis in hLECs. Because AOP2 protects hyperglycemia-induced hLEC apoptosis, this molecule may have the potential to prevent hyperglycemia-mediated complications in diabetes.
Collapse
Affiliation(s)
- E Kubo
- Department of Ophthalmology, Fukui Medical University, Fukui, Japan
| | | | | | | | | |
Collapse
|
|
41
|
Ong MD, Payne DM, Garner MH. Differential protein expression in lens epithelial whole-mounts and lens epithelial cell cultures. Exp Eye Res 2003; 77:35-49. [PMID: 12823986 DOI: 10.1016/s0014-4835(03)00090-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE Lens fibergenesis is a problem in several types of cataract and in the posterior capsular opacification following cataract surgery. To correct improper fiber differentiation or to prevent unwanted growth on the posterior capsule following cataract surgery requires a thorough understanding of normal and abnormal fiber formation. To this end, studies were initiated to characterize fiber differentiation in the bovine lens and in lens epithelial cell cultures. METHODS Indirect immunofluorescence and immunoblot analysis were employed to study the expression of vimentin, beta-crystallin, gamma-crystallin, filensin, aquaporin 0 and the Na, K-ATPase catalytic subunit isoforms (alpha1, alpha2, alpha3) in bovine lens epithelium whole-mounts as well as lens epithelial cell cultures propagated in medium containing 10% bovine serum or in medium supplemented with bovine serum concentrations < or =4%. RESULTS Three distinct cell types were observed in the bovine lens epithelium. The cells of the central zone were identified by a polarized distribution of two distinct Na, K-ATPase catalytic subunit isoforms, alpha1 to the apical (fiber side) and alpha3 to the basal (aqueous humor side) membranes. Lateral to the polarized central zone, was the germinative zone of cells, best characterized by perinuclear vimentin basket-like structures and the loss of polarized Na, K-ATPase catalytic subunit isoforms. Lateral to the germinative zone were the cells of the transition zone (meridinal rows) where expression of the lens specific proteins beta-crystallin, gamma-crystallin, filensin and aquaporin 0 as well as the lens fiber-, adipocyte- and brain glia-specific Na, K-ATPase catalytic subunit, alpha2 are expressed. The cultured cells propagated in medium supplemented with 10% serum bore no resemblance to any of the cells of the bovine lens epithelium whole-mounts. The cells propagated in the medium supplemented with the lower bovine serum levels resembled the differentiating fibers of the transition zone of the bovine lens epithelium whole-mounts as well as superficial cortical fibers. CONCLUSIONS Since the low-serum lens epithelial cell cultures bear a remarkable resemblance to early differentiating fibers, they are reasonable models for the study of early fiber differentiation or prevention of differentiation. The culture conditions employed do not yield the polarized cells of the central zone. Nor has the function of these polarized cells in lens fluid, nutrient and ion homeostasis been determined.
Collapse
Affiliation(s)
- Marcia D Ong
- Department of Pathology and Anatomy, Division of Cell Biology and Genetics, UNT Health Science Center, Fort Worth, TX 76107, USA
| | | | | |
Collapse
|