stilbenes and Glaucoma

Resveratrol (3,5,4'-trans-trihydroxystilbene) is a polyphenolic phytoalexin belonging to the stilbene family. It is commonly found in grape skins and seeds, as well as other plant-based foods. Oxidative stress and inflammation play a key role in the initiation and progression of age-related eye disorders (glaucoma, cataracts, diabetic retinopathy, and macular degeneration) that lead to a progressive loss of vision and blindness. Even though the way resveratrol affects the human body and the course of many diseases is still the subject of ongoing scientific research, it has been shown that the broad spectrum of anti-inflammatory and neuroprotective properties of resveratrol has a beneficial effect on eye tissues. In our research, we decided to analyze the current scientific literature on resveratrol, its possible mechanisms of action, and its therapeutic application in order to assess its effectiveness in eye diseases.

Topics: Antioxidants; Glaucoma; Humans; Oxidative Stress; Resveratrol; Stilbenes

Low vision and blindness are important health problems that affect millions of people throughout the world. The most common and important pathologies are diabetic retinopathy, age-related macular degeneration, glaucoma as well as cataracts. The latter consists of an opacification of the lens of the eye which impedes the passage of light and represents one of the most important causes of vision loss. Among the risk factors for cataract development, there are life-style factors such as the use of tobacco, abuse of alcohol and unhealthy diet. In light of this, dietary components that possess anti-oxidant activity, such as polyphenols for instance, can be considered good candidates for human studies in the prevention and or treatment of such diseases. Among dietary components, the antioxidant capacity of certain polyphenols is well known, and these could be good candidates. In this review we focus our attention on the current scientific literature regarding to the effects of resveratrol on cataracts and other ocular diseases, along with its potential mechanism/s of action. A large number of preclinical studies support the involvement of resveratrol in clinical trials for the prevention and treatment of eye diseases induced by oxidative stress and inflammation, such as age-related cataract.

Topics: Animals; Antioxidants; Cataract; Glaucoma; Humans; Lipid Peroxidation; Oxidative Stress; Resveratrol; Stilbenes

Glaucoma is the leading cause of irreversible blindness in industrialized countries and comprises a group of diseases characterized by progressive optic nerve degeneration. Glaucoma is commonly associated with elevated intraocular pressure due to impaired outflow of aqueous humor resulting from abnormalities within the drainage system of the anterior chamber angle (open-angle glaucoma) or impaired access of aqueous humor to the drainage system (angle-closure glaucoma). Oxidative injury and altered antioxidant defense mechanisms in glaucoma appear to play a role in the pathophysiology of glaucomatous neurodegeneration that is characterized by death of retinal ganglion cells. Oxidative protein modifications occurring in glaucoma serve as immunostimulatory signals and alter neurosupportive and immunoregulatory functions of glial cells. Initiation of the apoptotic cascade observed in glaucomatous retinopathy can involve oxidant mechanisms and different agents have been shown to be neuroprotective. This review focuses on the molecular mechanisms of oxidant injury and summarizes studies that have investigated novel free radical scavengers in the treatment of glaucomatous neurodegeneration.

Topics: Animals; Antioxidants; Apoptosis; DNA; Free Radical Scavengers; Ginkgo biloba; Glaucoma; Humans; Lipid Peroxidation; Oxidative Stress; Protein Carbonylation; Resveratrol; Stilbenes; Sulfonamides; Thiophenes

To evaluate the effects of the neuroprotective agents riluzole and resveratrol on the survival of retinal ganglion cells (RGCs) when administered alone or in combination.. Experimental glaucoma was induced by injecting hyaluronic acid into the anterior chamber of Wistar albino rats weekly for a six-week period. Intraocular pressure was measured before and immediately after glaucoma induction. The neuroprotective effects of daily intraperitoneal injections of riluzole (8 mg/kg) and resveratrol (10 mg/kg) were evaluated and compared. After the six-week period, dextran tetramethylrhodamine was applied into the optic nerve and the density of surviving RGCs was evaluated by counting the labeled RGCs in whole mount retinas for retrograde labeling of RGCs.. The mean numbers of RGCs were significantly preserved in all treatment groups compared to the vehicle-treated glaucoma group (G). The mean number of RGCs in mm(2) were 1207 ± 56 in the control group (C), 404 ± 65 in G group, 965 ± 56 in riluzole-treated group in the early phase of glaucoma (E-Ri), 714 ± 25 in riluzole-treated group in the late phase of glaucoma (L-Ri), 735 ± 29 in resveratrol-treated group in the early phase of glaucoma (E-Re), 667 ± 20 in resveratrol-treated group in the late phase of glaucoma (L-Re), and 1071 ± 49 in riluzole and resveratrol combined-treated group in the early phase of glaucoma (E-RiRe group).. When used either alone or in combination, both riluzole and resveratrol, two agents with different mechanisms of action in glaucoma, significantly delayed RGC loss in this study's experimental glaucoma model.

Topics: Animals; Antioxidants; Cell Count; Cell Survival; Disease Models, Animal; Drug Therapy, Combination; Glaucoma; Injections, Intraperitoneal; Intraocular Pressure; Male; Neuroprotective Agents; Rats; Rats, Wistar; Resveratrol; Retinal Ganglion Cells; Riluzole; Stilbenes; Tonometry, Ocular

To study the relationship between SIRT1 and glaucoma trabecular meshwork cell (GTM) cell on DNA double-strand breaks (DSBs) repair capability and resist cellular senescence.. The expressions of SIRT1 in GTM and normal trabecular meshwork (HTM) cell detected by RT-RCR and Western blot; HTM and GTM cells divided into four groups separately: Res group (treat cells with 0.5 micromol/L Resveratrol for 24 h), SIRT1-ShRNA group (cells infected with recombinant SIRT1-ShRNA), microRNA34a group (cells infected with recombinant microRNA34a) and control group. The expression level of SIRT1 in groups was detected by Western blot. SA-beta-Gal staining was applied to each group of cells at 10 h, 32 h, 3 d and 6 d to evaluate the senescence of the cells. DSBs and the expression of gamma-H2AX after treated with 1.33 mol/L H2O2 at 0 h, 1 h, 2 h were detected by comet electrophoresis and Western blot.. The expression of SIRT1 were observed in both HTM and GTM cells, but the expression level in HTM was higher than that of GTM cells have the ability to express SIRT1, however the expression of SIRT1 was lower than HTM. Expression levels of SIRT1 presented following treads: Res > Control > microRNA34a > SIRT1-ShRNA. The dgree of senescence in GTM was higher than that in HTM cells when detected at the same time point with SA-beta-Gal staining. In the same cell line, the signs of senescence were appeared firstly and seriously in the cells treated with SIRT1-ShRNA in a time-dependent manner. Differently, after 24 h treatment with Res, the degree of senescence was decreased. The DSBs in GTM group was more than that of HTM group after treatment with oxidant when detected with Comet Electrophoresis and the the trends of the change was SIRT1-ShRNA > microRNA34a > Control > Res. The similar results also observed in the expression of gamma-H2AX.. SIRT1 may be useful in predicting the development and prognosis of glaucoma; Res promotes the expression of SIRT1 significantly, and the SIRT1 may protects GTM from oxidative stress-induced DSBs, aging even apoptosis, and promotes cell cycle arrest, which may provide a new target to treat glaucoma.

Topics: Cells, Cultured; Cellular Senescence; DNA Breaks, Double-Stranded; DNA Repair; Glaucoma; Humans; Hydrogen Peroxide; Oxidative Stress; Resveratrol; RNA, Small Interfering; Sirtuin 1; Stilbenes; Trabecular Meshwork

Elevated intraocular pressure (IOP) constitutes the best characterized risk for primary open-angle glaucoma (POAG). Elevated IOP is believed to result from an increase in aqueous humor outflow resistance at the level of the trabecular meshwork (TM)/Schlemm's canal. Malfunction of the TM in POAG is associated with the expression of markers for inflammation, cellular senescence, oxidative damage, and decreased cellularity. Current POAG treatments rely on lowering IOP, but there is no therapeutic approach available to delay the loss of function of the TM in POAG patients. We evaluated the effects of chronic administration of the dietary supplement resveratrol on the expression of markers for inflammation, oxidative damage, and cellular senescence in primary TM cells subjected to chronic oxidative stress (40% O2). Resveratrol treatment effectively prevented increased production of intracellular reactive oxygen species (iROS) and inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), and reduced expression of the senescence markers sa-beta-gal, lipofuscin, and accumulation of carbonylated proteins. Furthermore, resveratrol exerted antiapoptotic effects that were not associated with a decrease in cell proliferation. These results suggest that resveratrol could potentially have a role in preventing the TM tissue abnormalities observed in POAG.

Topics: Animals; Apoptosis; Biomarkers; Dose-Response Relationship, Drug; Glaucoma; Hydrogen Peroxide; Inflammation; Oxidative Stress; Oxygen; Reactive Oxygen Species; Resveratrol; Stilbenes; Swine; Trabecular Meshwork

Topics: Antidepressive Agents; Eye Diseases; Glaucoma; Humans; Intraocular Pressure; Pharmacology; Stilbenes; Tonometry, Ocular