scholarly journals Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

2020 ◽  
Vol 21 (3) ◽  
pp. 704 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Viktoriia E. Baksheeva ◽  
Veronika V. Tiulina ◽  
Sergei V. Goriainov ◽  
Nadezhda V. Azbukina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Aqueous Humor ◽  
Rabbit Model ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Cyclooxygenase Inhibitor ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.

scholarly journals Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation

2018 ◽  
Vol 19 (7) ◽  
pp. 2118 ◽  
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Maria Mazzone ◽  
Francesco Giuliano ◽  
Guido Basile ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment ◽  
Sirtuin 1 ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
P Values ◽  
Sirt1 Expression ◽  
Inflammatory Conditions ◽  
Age Related ◽  
Retinal Degenerative Diseases

The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, including age-related macular degeneration (AMD), has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may modulate DNMT and SIRT1 functions and restore changes in LINE-1 methylation. Cells were treated with 25 mU/mL glucose oxidase (GOx) or 10 µg/mL lipopolysaccharide (LPS) to mimic oxidative or inflammatory conditions, respectively. Oxidative stress decreased DNMT1, DNMT3a, DNMT3b, and SIRT1 expression (p-values < 0.05), as well as total DNMTs (−28.5%; p < 0.0001) and SIRT1 (−29.0%; p < 0.0001) activities. Similarly, inflammatory condition decreased DNMT1 and SIRT1 expression (p-values < 0.05), as well as total DNMTs (−14.9%; p = 0.007) and SIRT1 (−20.1%; p < 0.002) activities. Interestingly, GOx- and LPS-treated cells exhibited lower LINE-1 methylation compared to controls (p-values < 0.001). We also demonstrated that treatment with 10 μM resveratrol for 24 h counteracted the detrimental effect on DNMT and SIRT1 functions, and LINE-1 methylation, in cells under oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of retinal degenerative diseases.

scholarly journals The Role of Inflammation in Retinal Neurodegeneration and Degenerative Diseases

2021 ◽  
Vol 23 (1) ◽  
pp. 386
Author(s):  
Geetika Kaur ◽  
Nikhlesh K. Singh
Keyword(s):  
Retinal Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Treatment Modalities ◽  
Macular Dystrophy ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Neurodegeneration ◽  
Retinal Degenerative Diseases

Retinal neurodegeneration is predominantly reported as the apoptosis or impaired function of the photoreceptors. Retinal degeneration is a major causative factor of irreversible vision loss leading to blindness. In recent years, retinal degenerative diseases have been investigated and many genes and genetic defects have been elucidated by many of the causative factors. An enormous amount of research has been performed to determine the pathogenesis of retinal degenerative conditions and to formulate the treatment modalities that are the critical requirements in this current scenario. Encouraging results have been obtained using gene therapy. We provide a narrative review of the various studies performed to date on the role of inflammation in human retinal degenerative diseases such as age-related macular degeneration, inherited retinal dystrophies, retinitis pigmentosa, Stargardt macular dystrophy, and Leber congenital amaurosis. In addition, we have highlighted the pivotal role of various inflammatory mechanisms in the progress of retinal degeneration. This review also offers an assessment of various therapeutic approaches, including gene-therapies and stem-cell-based therapies, for degenerative retinal diseases.

scholarly journals Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Maria H. Madeira ◽  
Raquel Boia ◽  
Paulo F. Santos ◽  
António F. Ambrósio ◽  
Ana R. Santiago
Keyword(s):  
Vision Loss ◽  
Neuronal Loss ◽  
Age Related Macular Degeneration ◽  
Therapeutic Interventions ◽  
Degenerative Diseases ◽  
Disease Etiology ◽  
Neurodegenerative Process ◽  
Age Related ◽  
Retinal Microglia ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

scholarly journals The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Borut Poljšak ◽  
Rok Fink
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Environmental Pollutants ◽  
Protective Role ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Age Related ◽  
Dietary Antioxidant ◽  
Polycyclic Aromatic ◽  
Antioxidant Supplements

Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example,β-carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants.

scholarly journals Perspectives of Stem Cell–Based Therapy for Age-Related Retinal Degenerative Diseases

2017 ◽  
Vol 26 (9) ◽  
pp. 1538-1541 ◽  
Author(s):  
Vladimir Holan ◽  
Barbora Hermankova ◽  
Jan Kossl
Keyword(s):  
Stem Cell ◽  
Treatment Protocol ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Cell Type ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell–based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.

scholarly journals Protective Effects of Curcumin Ester Prodrug, Curcumin Diethyl Disuccinate against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells: Potential Therapeutic Avenues for Age-Related Macular Degeneration

2019 ◽  
Vol 20 (13) ◽  
pp. 3367 ◽  
Author(s):  
Chawanphat Muangnoi ◽  
Umar Sharif ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Pornchai Rojsitthisak ◽  
Luminita Paraoan
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Parent Drug ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Rpe Cells ◽  
Age Related ◽  
Potent Drug

Oxidative stress-induced damage to the retinal pigmented epithelium (RPE), a specialised post-mitotic monolayer that maintains retinal homeostasis, contributes to the development of age-related macular degeneration (AMD). Curcumin (Cur), a naturally occurring antioxidant, was previously shown to have the ability to protect RPE cells from oxidative stress. However, poor solubility and bioavailability makes Cur a poor therapeutic agent. As prodrug approaches can mitigate these limitations, we compared the protective properties of the Cur prodrug curcumin diethyl disuccinate (CurDD) against Cur in relation to oxidative stress induced in human ARPE-19 cells. Both CurDD and Cur significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Both drugs exerted their protective effects through the modulation of p44/42 (ERK) and the involvement of downstream molecules Bax and Bcl-2. Additionally, the expression of antioxidant enzymes HO-1 and NQO1 was also enhanced in cells treated with CurDD and Cur. In all cases, CurDD was more effective than its parent drug against oxidative stress-induced damage to ARPE-19 cells. These findings highlight CurDD as a more potent drug compared to Cur against oxidative stress and indicate that its protective effects are exerted through modulation of key apoptotic and antioxidant molecular pathways.

scholarly journals Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 920
Author(s):  
Ayana Suzumura ◽  
Ryo Terao ◽  
Hiroki Kaneko
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Essential Fatty Acids ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Retinal Diseases ◽  
Protective Effects ◽  
Molecular Signaling ◽  
Age Related ◽  
Membrane Components

Oxidative stress and inflammation play crucial roles in the development and progression of retinal diseases. Retinal damage by various etiologies can result in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD). n-3 fatty acids are essential fatty acids and are necessary for homeostasis. They are important retinal membrane components and are involved in energy storage. n-3 fatty acids also have antioxidant and anti-inflammatory properties, and their suppressive effects against ROP, DR, and AMD have been previously evaluated. α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites have been shown to alleviate retinal oxidative stress and inflammation involving various biological signaling pathways. In this review, we summarize the current understanding of the n-3 fatty acids effects on the mechanisms of these retinal diseases and how they exert their therapeutic effects, focusing on ALA, EPA, DHA, and their metabolites. This knowledge may provide new remedial strategies for n-3 fatty acids in the prevention and treatment of retinal diseases associated with oxidative stress and inflammation.

Vascular Inflammation Risk Factors in Retinal Disease

2019 ◽  
Vol 5 (1) ◽  
pp. 99-122 ◽  
Author(s):  
Ileana Soto ◽  
Mark P. Krebs ◽  
Alaina M. Reagan ◽  
Gareth R. Howell
Keyword(s):  
Vascular Inflammation ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Future Research ◽  
Primary Role ◽  
Degenerative Diseases ◽  
Age Related ◽  
The Central Nervous System ◽  
Retinal Degenerative Diseases ◽  
Underlying Mechanisms

Inflammation of the blood vessels that serve the central nervous system has been increasingly identified as an early and possibly initiating event among neurodegenerative conditions such as Alzheimer's disease and related dementias. However, the causal relevance of vascular inflammation to major retinal degenerative diseases is unresolved. Here, we describe how genetics, aging-associated changes, and environmental factors contribute to vascular inflammation in age-related macular degeneration, diabetic retinopathy, and glaucoma. We highlight the importance of mouse models in studying the underlying mechanisms and possible treatments for these diseases. We conclude that data support vascular inflammation playing a central if not primary role in retinal degenerative diseases, and this association should be a focus of future research.

scholarly journals The Protective Effects of α-Mangostin Attenuate Sodium Iodate-Induced Cytotoxicity and Oxidative Injury via Mediating SIRT-3 Inactivation via the PI3K/AKT/PGC-1α Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1870
Author(s):  
Chen-Ju Chuang ◽  
Meilin Wang ◽  
Jui-Hsuan Yeh ◽  
Tzu-Chun Chen ◽  
Shang-Chun Tsou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Cell Damage ◽  
Outer Nuclear Layer ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Age Related

It is well known that age-related macular degeneration (AMD) is an irreversible neurodegenerative disease that can cause blindness in the elderly. Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a part of the pathogenesis of AMD. In this study, we evaluated the protective effect and mechanisms of alpha-mangostin (α-mangostin, α-MG) against NaIO3-induced reactive oxygen species (ROS)-dependent toxicity, which activates apoptosis in vivo and in vitro. MTT assay and flow cytometry demonstrated that the pretreatment of ARPE-19 cells with α-MG (0, 3.75, 7.5, and 15 μM) significantly increased cell viability and reduced apoptosis from NaIO3-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cleaved PARP-1, cleaved caspase-3 protein expression, and enhancement of Bcl-2 protein. Furthermore, pre-incubation of ARPE-19 cells with α-MG markedly inhibited the intracellular ROS and extracellular H2O2 generation via blocking of the abnormal enzyme activities of superoxide dismutase (SOD), the downregulated levels of catalase (CAT), and the endogenous antioxidant, glutathione (GSH), which were regulated by decreasing PI3K-AKT-PGC-1α-STRT-3 signaling in ARPE-19 cells. In addition, our in vivo results indicated that α-MG improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer by inhibiting the expression of cleaved caspase-3 protein. Taken together, our results suggest that α-MG effectively protects human ARPE-19 cells from NaIO3-induced oxidative damage via antiapoptotic and antioxidant effects.

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