Oxidative Stress in Retinal Degeneration

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 14977

Special Issue Editors

School of Optometry & Vision Science, University of New South Wales, Sydney, NSW 2052, Australia
Interests: human retina; RPE and choroid ageing; eye melanoma; inflammation; ocular surface health
Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2008, Australia
Interests: cell culture; western blot analysis; PCR; gel electrophoresis; immunofluorescence; SDS-PAGE cloning; flow cytometry; DNA; DNA extraction
John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia
Interests: human retina; immunofluorescence; flow cytometry; eye melanoma; inflammation; PCR
John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia
Interests: vision science; cell physiology; central nervous system; cell metabolism; sensory systems; ophthalmology; cell development, proliferation and death

Special Issue Information

Dear Colleagues,

The retina and retinal pigmented epithelium (RPE) are exposed to high levels of light associated with the activation of phototransduction pathways, and accompanied by very high levels of oxygen consumption and aerobic glycolysis, with the generation of high levels of reactive oxygen species (ROS). Normally the impacts of ROS and oxidative stress are ‘managed’ via antioxidant activity. The cumulative effects of oxidative stress may compromise the blood–retinal barrier (inner and outer), induce chronic inflammation and tissue damage, and are implicated in retinal degenerations such as age-related macular degeneration, inherited retinal dystrophies, and diabetic retinopathy. Owing to the central role of oxidative stresss in retinal pathologies, the therapeutic potential of anti-oxidant molecules is currently subject to intense research.

In this Special Issue, we welcome original research articles and brief reports, reviews, new methods, and clinical trial outcomes that are relevant to better understanding the effects of oxidative stress and metabolic dysfunction on the underlying pathogenesis of retinal degenerations, including (but not limited to) age-related macular degeneration, inherited retinal degenerations, and diabetic retinopathy. This may include studies on underlying cell signalling pathways, clinical imaging, and electrophysiology to identify early signs of oxidative stress and retinal degeneration, as well as potential therapeutic approaches to mitigate or control oxidative stress-induced retinal pathology.

Prof. Dr. Michele C. Madigan
Dr. Ting Zhang
Dr. Adrian V. Cioanca
Dr. Riccardo Natoli
Guest Editors

Manuscript Submission Information

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Keywords

  • retinal pigment epithelium
  • retinal degeneration
  • age-related macular degeneration
  • light damage
  • mitochondrial dysfunction
  • metabolism
  • inflammation
  • reactive oxygen species

Published Papers (8 papers)

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Research

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30 pages, 12295 KiB  
Article
Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice
by Seyed Mohamadmehdi Moshtaghion, Estefanía Caballano-Infantes, Álvaro Plaza Reyes, Lourdes Valdés-Sánchez, Patricia Gallego Fernández, Berta de la Cerda, Maurizio S. Riga, Manuel Álvarez-Dolado, Pablo Peñalver, Juan C. Morales and Francisco J. Díaz-Corrales
Antioxidants 2024, 13(2), 201; https://doi.org/10.3390/antiox13020201 - 04 Feb 2024
Viewed by 960
Abstract
Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell [...] Read more.
Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown that resveratrol (RSV) is a promising molecule that can mitigate PARP1 overactivity, but its low bioavailability is a limitation for medical use. This study examined the impact of a synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), in the 661W cell line against H2O2 oxidative stress and in rd10 mice. PIC-OCT possesses a better ADME profile than RSV. In response to H2O2, 661W cells pretreated with PIC-OCT preserved cell viability in more than 38% of cells by significantly promoting SIRT1 nuclear translocation, preserving NAD+/NADH ratio, and suppressing intracellular ROS formation. These effects result from expressing antioxidant genes, maintaining mitochondrial function, reducing PARP1 nuclear expression, and preventing AIF nuclear translocation. In rd10 mice, PIC-OCT inhibited PAR-polymer formation, increased SIRT1 expression, significantly reduced TUNEL-positive cells in the retinal outer nuclear layer, preserved ERGs, and enhanced light chamber activity (all p values < 0.05). Our findings corroborate that PIC-OCT protects photoreceptors by modulating the SIRT1/PARP1 axis in models of retinal degeneration. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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13 pages, 3998 KiB  
Article
Oxidative and Endoplasmic Reticulum Stress Represent Novel Therapeutic Targets for Choroideremia
by Hajrah Sarkar, Manuela Lahne, Neelima Nair and Mariya Moosajee
Antioxidants 2023, 12(9), 1694; https://doi.org/10.3390/antiox12091694 - 30 Aug 2023
Viewed by 1130
Abstract
Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy, affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, with no approved therapy. CHM is caused by mutations in the CHM gene, which encodes the ubiquitously expressed Rab escort protein 1 (REP1). REP1 is involved [...] Read more.
Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy, affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, with no approved therapy. CHM is caused by mutations in the CHM gene, which encodes the ubiquitously expressed Rab escort protein 1 (REP1). REP1 is involved in prenylation, a post-translational modification of Rab proteins, and plays an essential role in intracellular trafficking. In this study, we examined oxidative and endoplasmic reticulum (ER) stress pathways in chmru848 zebrafish and CHMY42X patient fibroblasts, and screened a number of neuroprotectants for their ability to reduce stress. The expression of the oxidative stress markers txn, cat and sod3a, and the ER stress markers bip, atf4 and atf6, were dysregulated in chmru848 fish. The expression of SOD2 was also reduced in CHMY42X fibroblasts, along with reduced BIP and increased CHOP expression. The lack of REP1 is associated with defects in vesicular trafficking, photoreceptor outer segment phagocytosis and melanosome transport, leading to increased levels of stress within the retina and RPE. Drugs targeting oxidative and ER stress pathways represent novel therapeutic avenues. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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17 pages, 3757 KiB  
Article
Exogenous CFH Modulates Levels of Pro-Inflammatory Mediators to Prevent Oxidative Damage of Retinal Pigment Epithelial Cells with the At-Risk CFH Y402H Variant
by Henry Velazquez-Soto, Sergio Groman-Lupa, Marisa Cruz-Aguilar, Alberto L. Salazar, Juan C. Zenteno and Maria C. Jimenez-Martinez
Antioxidants 2023, 12(8), 1540; https://doi.org/10.3390/antiox12081540 - 31 Jul 2023
Viewed by 1157
Abstract
Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and [...] Read more.
Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and oxidative stress have been implicated in AMD pathogenesis. Oxidative stress causes RPE injury, resulting in a chronic inflammatory response and cell death. The Y402H polymorphism in the complement factor H (CFH) protein is an important risk factor for AMD. However, the functional significance of CFH Y402H polymorphism remains unclear. In the present study, we investigated the role of CFH in the pro-inflammatory response using an in vitro model of oxidative stress in the RPE with the at-risk CFH Y402H variant. ARPE-19 cells with the at-risk CFH Y402H variant were highly susceptible to damage caused by oxidative stress, with increased levels of inflammatory mediators and pro-apoptotic factors that lead to cell death. Pretreatment of the ARPE-19 cell cultures with exogenous CFH prior to the induction of oxidative stress prevented damage and cell death. This protective effect may be related to the negative regulation of pro-inflammatory cytokines. CFH contributes to cell homeostasis and is required to modulate the pro-inflammatory cytokine response under oxidative stress in the ARPE-19 cells with the at-risk CFH Y402H variant. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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17 pages, 3185 KiB  
Article
Matrix Metalloproteinase 13 Is Associated with Age-Related Choroidal Neovascularization
by Jorge González-Zamora, María Hernandez, Sergio Recalde, Jaione Bezunartea, Ana Montoliu, Valentina Bilbao-Malavé, Sara Llorente-González, Alfredo García-Layana and Patricia Fernández-Robredo
Antioxidants 2023, 12(4), 884; https://doi.org/10.3390/antiox12040884 - 05 Apr 2023
Viewed by 1238
Abstract
Age-related macular degeneration (AMD) is a leading cause of severe vision loss in older individuals in developed countries. Despite advances in our understanding of AMD, its pathophysiology remains poorly understood. Matrix metalloproteinases (MMPs) have been proposed to play a role in AMD development. [...] Read more.
Age-related macular degeneration (AMD) is a leading cause of severe vision loss in older individuals in developed countries. Despite advances in our understanding of AMD, its pathophysiology remains poorly understood. Matrix metalloproteinases (MMPs) have been proposed to play a role in AMD development. In this study, we aimed to characterize MMP-13 in AMD. We used retinal pigment epithelial cells, a murine model of laser-induced choroidal neovascularization, and plasma samples from patients with neovascular AMD to conduct our study. Our results show that MMP13 expression significantly increased under oxidative stress conditions in cultured retinal pigment epithelial cells. In the murine model, MMP13 was overexpressed in both retinal pigment epithelial cells and endothelial cells during choroidal neovascularization. Additionally, the total MMP13 levels in the plasma of patients with neovascular AMD were significantly lower than those in the control group. This suggests a reduced diffusion from the tissues or release from circulating cells in the bloodstream, given that the number and function of monocytes have been reported to be deficient in patients with AMD. Although more studies are needed to elucidate the role of MMP13 in AMD, it could be a promising therapeutic target for treating AMD. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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17 pages, 6206 KiB  
Article
P2X7 Is Involved in the Mouse Retinal Degeneration via the Coordinated Actions in Different Retinal Cell Types
by Ponarulselvam Sekar, George Hsiao, Yuan-Shen Chen, Wan-Wan Lin and Chi-Ming Chan
Antioxidants 2023, 12(1), 141; https://doi.org/10.3390/antiox12010141 - 06 Jan 2023
Cited by 4 | Viewed by 2125
Abstract
Adenosine triphosphate (ATP) released from dying cells with high concentrations is sensed as a danger signal by the P2X7 receptor. Sodium iodate (NaIO3) is an oxidative toxic agent, and its retinal toxicity has been used as the model of dry age-related [...] Read more.
Adenosine triphosphate (ATP) released from dying cells with high concentrations is sensed as a danger signal by the P2X7 receptor. Sodium iodate (NaIO3) is an oxidative toxic agent, and its retinal toxicity has been used as the model of dry age-related macular degeneration (AMD). In this study, we used NaIO3-treated mice and cultured retinal cells, including BV-2 microglia, 661W photoreceptors, rMC1 Müller cells and ARPE-19 retinal epithelial cells, to understand the pathological action of P2X7 in retinal degeneration. We found that NaIO3 can significantly decrease the photoreceptor function by reducing a-wave and b-wave amplitudes in electroretinogram (ERG) analysis. Optical coherence tomography (OCT) analysis revealed the degeneration of retinal epithelium and ganglion cell layers. Interestingly, P2X7−/− mice were protected from the NaIO3-induced retinopathy and inflammatory NLRP3, IL-1β and IL-6 gene expression in the retina. Hematoxylin and eosin staining indicated that the retinal epithelium was less deteriorated in P2X7−/− mice compared to the WT group. Although P2X7 was barely detected in 661W, rMC1 and ARPE-19 cells, its gene and protein levels can be increased after NaIO3 treatment, leading to a synergistic cytotoxicity of BzATP [2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate tri(triethyleneammonium)salt] and NaIO3 administration in ARPE-19 cells. In conclusion, the paracrine action of the ATP/P2X7 axis via cell–cell communication is involved in NaIO3-induced retinal injury. Our results show that P2X7 antagonist might be a potential therapy in inflammation-related retinal degeneration. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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19 pages, 5093 KiB  
Article
Ginkgo biloba Extract Attenuates Light-Induced Photoreceptor Degeneration by Modulating CAV-1—Redoxosome Signaling
by Ke Wang, Yuan Chen, Xue Zhu, Wenjun Zou and Fanfan Zhou
Antioxidants 2022, 11(7), 1268; https://doi.org/10.3390/antiox11071268 - 27 Jun 2022
Cited by 3 | Viewed by 2210
Abstract
The clinical potential of Ginkgo biloba extract (GBE) in the prevention and/or treatment of retinal degenerative diseases has been widely explored; however, the underlying molecular mechanism is poorly understood. Photoreceptor degeneration is the hallmark of retinal degenerative diseases and leads to vision impairment [...] Read more.
The clinical potential of Ginkgo biloba extract (GBE) in the prevention and/or treatment of retinal degenerative diseases has been widely explored; however, the underlying molecular mechanism is poorly understood. Photoreceptor degeneration is the hallmark of retinal degenerative diseases and leads to vision impairment or loss. In this study, the effect of GBE against white light (WL) illumination-induced photoreceptor degeneration was investigated, as well as its underlying mechanism. To evaluate the in vitro activity of GBE, analysis of cell viability, cell apoptosis, oxidative stress, NOX (NADH oxidase) activity and mitochondrial membrane potential (MMP), as well as Western blotting and transcriptome sequencing and analysis, were conducted. To evaluate the in vivo activity of GBE, HE staining, electroretinography (ERG), Terminal-deoxynucleoitidyl transferase (TdT)-mediated nick end labeling (TUNEL) assay and immunofluorescence analysis were conducted. Our study showed that GBE treatment significantly attenuated WL illumination-induced oxidative damage in photoreceptor 661W cells—a finding that was also verified in C57BL/6J mice. Further molecular study revealed that WL illumination downregulated caveolin-1 (CAV-1) expression, interrupted CAV-1-NOX2 interaction, re-located NOX2 from the cell membrane to the cytoplasm and induced the formation of redoxosomes, which led to cell death. However, these cytotoxic events were significantly alleviated by GBE treatment. Interestingly, CAV-1 overexpression showed a consistent protective effect with GBE, while CAV-1 silencing impacted the protective effect of GBE against WL illumination-induced oxidative damage in in vitro and in vivo models. Thus, GBE was identified to prevent photoreceptor cell death due to CAV-1-dependent redoxosome activation, oxidative stress and mitochondrial dysfunction resulting from WL illumination. Overall, our study reveals the protective effect of GBE on photoreceptors against WL illumination-induced oxidative damage in in vitro and in vivo models, which effect is mediated through the modulation of CAV-1-redoxosome signaling. Our findings contribute to better understanding the therapeutic effect of GBE in preventing photoreceptor degeneration in retinal degenerative diseases, and GBE may become a novel therapeutic agent that is effective in reducing the morbidity of these diseases. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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Review

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27 pages, 2021 KiB  
Review
New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy
by Gustavo Bernardes Fanaro, Marcelo Rodrigues Marques, Karin da Costa Calaza, Rafael Brito, André Moreira Pessoni, Henrique Rocha Mendonça, Deborah Emanuelle de Albuquerque Lemos, José Luiz de Brito Alves, Evandro Leite de Souza and Marinaldo Pacífico Cavalcanti Neto
Antioxidants 2023, 12(6), 1237; https://doi.org/10.3390/antiox12061237 - 08 Jun 2023
Cited by 2 | Viewed by 1637
Abstract
Diabetic retinopathy (DR) is a neurodegenerative and vascular pathology that is considered one of the leading causes of blindness worldwide, resulting from complications of advanced diabetes mellitus (DM). Current therapies consist of protocols aiming to alleviate the existing clinical signs associated with microvascular [...] Read more.
Diabetic retinopathy (DR) is a neurodegenerative and vascular pathology that is considered one of the leading causes of blindness worldwide, resulting from complications of advanced diabetes mellitus (DM). Current therapies consist of protocols aiming to alleviate the existing clinical signs associated with microvascular alterations limited to the advanced disease stages. In response to the low resolution and limitations of the DR treatment, there is an urgent need to develop more effective alternative therapies to optimize glycemic, vascular, and neuronal parameters, including the reduction in the cellular damage promoted by inflammation and oxidative stress. Recent evidence has shown that dietary polyphenols reduce oxidative and inflammatory parameters of various diseases by modulating multiple cell signaling pathways and gene expression, contributing to the improvement of several chronic diseases, including metabolic and neurodegenerative diseases. However, despite the growing evidence for the bioactivities of phenolic compounds, there is still a lack of data, especially from human studies, on the therapeutic potential of these substances. This review aims to comprehensively describe and clarify the effects of dietary phenolic compounds on the pathophysiological mechanisms involved in DR, especially those of oxidative and inflammatory nature, through evidence from experimental studies. Finally, the review highlights the potential of dietary phenolic compounds as a prophylactic and therapeutic strategy and the need for further clinical studies approaching the efficacy of these substances in DR management. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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17 pages, 354 KiB  
Review
Metabolism Dysregulation in Retinal Diseases and Related Therapies
by Yingying Chen, Nathan J. Coorey, Meixia Zhang, Shaoxue Zeng, Michele C. Madigan, Xinyuan Zhang, Mark C. Gillies, Ling Zhu and Ting Zhang
Antioxidants 2022, 11(5), 942; https://doi.org/10.3390/antiox11050942 - 11 May 2022
Cited by 8 | Viewed by 3336
Abstract
The human retina, which is part of the central nervous system, has exceptionally high energy demands that requires an efficient metabolism of glucose, lipids, and amino acids. Dysregulation of retinal metabolism disrupts local energy supply and redox balance, contributing to the pathogenesis of [...] Read more.
The human retina, which is part of the central nervous system, has exceptionally high energy demands that requires an efficient metabolism of glucose, lipids, and amino acids. Dysregulation of retinal metabolism disrupts local energy supply and redox balance, contributing to the pathogenesis of diverse retinal diseases, including age-related macular degeneration, diabetic retinopathy, inherited retinal degenerations, and Macular Telangiectasia. A better understanding of the contribution of dysregulated metabolism to retinal diseases may provide better therapeutic targets than we currently have. Full article
(This article belongs to the Special Issue Oxidative Stress in Retinal Degeneration)
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