Resveratrol (RSV), a polyphenol compound made by plants to fight off fungal infections and other invaders, has been touted for its healing and protective qualities against conditions such as cancer and heart disease. With these restorative properties in mind, a new study in the International Journal of Molecular Sciences suggests RSV can also be highly effective in combating eye conditions, including age-related macular degeneration (AMD), glaucoma, cataract, diabetic retinopathy, proliferative vitreoretinopathy and corneal infection.1
The study, a literature review by a team of international researchers, cites RSV’s ability to act on common targets such as reactive oxygen species, lipid mediators, apoptosis, pro-inflammatory mediators and angiogenesis to prevent age-related ocular diseases. Additionally, the authors report RSV has innate properties that protect eyes against environmental factors such as diabetes, hypertension, stress, UV light, acrolein found in cigarette smoke and air pollution.1
Found naturally in red wines, Japanese knotweed roots, black currants, grape juices, peanuts and certain berries, RSV is hailed for its healing powers, not to mention its ability to modulate various targets in numerous pathologies. “Its properties have been shown to fight inflammation or inhibit inflammation and oxidation of certain cells, and it’s been found in studies to prevent cell death, or apoptosis,” says Paul Karpecki, OD.
“We’ve had some good results with RSV and cataracts, particularly in diabetic and aging cataracts,” Jeffrey Anshel, OD, adds. He explains that RSV activates the survival gene, Sirtuin 1 (SIRT1). “That’s where the anti-aging part of RSV comes in. It helps to activate the survival gene,” Dr. Anshel says.
RSV and AMD
The research paper purports RSV can battle specific AMD hallmarks, including oxidative damage, impaired retinal pigment epithelium (RPE), increased apoptosis, chronic inflammation and neovascularization.1
Various environmental factors produce free radicals, which lead to oxidative stress in ocular tissues and consequently provoke the initiation of diseases such as AMD. The investigators suggest RSV is able to scavenge free radicals (O2-) and activate superoxide dismutase or glutathione reductase, while also inhibiting inflammation through the reduction of various pro-inflammatory cytokines and blocking the signaling pathway induced by vascular endothelial growth factor-A to promote neo-angiogenesis.1
One study in the literature review found treatment with 50μmol/L and 100μmol/L RSV significantly reduced proliferation of RPE cells by 10% and 25%, respectively. Additionally, RSV (100μmol/L) inhibited basal and H2O2-induced intracellular oxidation and protected RPE cells from H2O2-induced cell death.2
Looking at inflammation, the study cited one investigation that showed RSV reduced the production of IL-6 and IL-8 induced by glucose in retinal cells, which is significant as the latter is an important risk factor for AMD.3
RSV and Glaucoma
Oxidative stress is known to be an early hallmark sign of hydrostatic pressure-induced retinal ganglion cell damage in glaucoma. Several studies have shown that oxygen metabolism and, more specifically, reactive oxygen species are crucial in the development of glaucoma. RSV has antioxidant properties that, through its hydroxyl groups, have the ability to react with reactive oxygen species in glaucoma.1
Trans-RSV activates sirtuin, which leads to the phosphorylation of Akt and inhibits Bax activity. RSV also activates the AMPK pathway, which leads to mitochondrial DNA transcription and replication. RSV is also able to alter Oma-1 and Yeme-1 mRNA expression, leading to the alteration of the long optical autophagy 1/short optical autophagy (L-Opa-1/S-Opa-1) ratio.1
In addition, RSV lowers reactive oxygen specie levels not only by activating the scavenger pathway, but also by facilitating the translocation of Nrf2 into the nucleus, thereby favoring interaction between Nfr2 and the antioxidant response element leading to HO production.1
RSV and Cataract
In an experimental model of naphthalene-induced age-related cataract in rats, RSV (20mg/kg and 40mg/kg per day IP) slowed lenticular opacity, restored antioxidants, Ca2+ ATPase function and protein content and reduced lipid peroxidation in the lenses of RSV-treated rats.4
Another study in the review found RSV could counter posterior capsule opacification-related physiological events in two human lens model systems.5
Dr. Karpecki cites yet another investigation not part of the current review that also looked at the effects of RSV on cataracts in a rat model. In this investigation, the rats either received subcutaneous injection of selenite, which induces advanced cataract within 24 hours, saline or a combination of sodium seleneite and 40mg of RSV. As expected, the rats injected by saline had clear eyes and the ones exposed to pure selenite had higher-grade cataracts. In the rats that received the RSV/selenite combination, only nine out of the 16 developed cataracts, which were of a lower grade.6
RSV and Diabetic Retinopathy
The authors also suggest RSV can combat diabetic retinopathy, since RSV activates SIRT1, which leads to the phosphorylation of Akt and inhibits the mitochondrial apoptosis pathway. Additionally, RSV stimulates mitochondrial activity through the AMPK–PGC1α pathway, which reduces apoptosis. RSV also lowers ROS through the iPf2α, AGE/RAGE, PKC and polyol pathways and downregulates pro-inflammatory cytokines such as IL-1β, IL-6 and IL-8, the researchers said.1
Other Ocular Benefits
Dr. Karpecki cites another study that found both red wine polyphenolic compounds and green tea polyphenols were able to inhibit several key events of the angiogenic process, such as the proliferation and migration of endothelial cells and vascular smooth muscle cells and the expression of two major proangiogenic factors, vascular endothelial growth factor and matrix metalloproteinase-2, by both redox-sensitive and redox-insensitive mechanisms.7
Antiangiogenic properties of polyphenols have also been observed in the chick embryo chorioallantoic membrane since the local application of RWPCs and GTPs strongly inhibits the formation of new blood vessels. Moreover, intake of RSV or green tea has been shown to reduce corneal neovascularization induced by proangiogenic factors such as VEGF and fibroblast growth factor in mice.7
RSV in Practice
Despite RSV’s good marks in the literature, this doesn’t mean ODs should suggest their patients consume wine to ward off eye disease, experts caution.
While wine in moderation has proved to be beneficial in some cases, Dr. Karpecki stresses that RSV can be found in other forms, including grape seed extract, black currants and certain supplements.
“If you look at the amount of RSV in wine, it’s pretty minimal. What I specifically tell people is, ‘You’ll only need 14 glasses of wine a day to get enough RSV,’” Dr. Anshel says with a laugh. “You’re actually better off taking a supplement with RSV in it.”
Dr. Anshel notes there are many supplements on the market, including an RSV combination with vitamin D and rice bran that helps with bioavailability.
One study that looked at the effects of the OTC supplement over a several-year period showed broad bilateral improvements in ocular structure and function in three AMD patients, including one with a treatment-resistant variant, which was opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology.8
Still, other OTC products contain GLA derived from black currant seed oil, a foundation of RSV, and can also combat dry eye.
1. Delmas D, Cornebise C, Courtaut F, et al. New highlights of resveratrol: a review of properties against ocular diseases. Int J Mol Sci. 2021;22(3):1295.
2. King RE, Kent KD, Bomser JA. Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition. Chem Biol Interact. 2005;151:143-9.
3. Losso JN, Truax RE, Richard G. Trans-resveratrol inhibits hyperglycemia-induced inflammation and connexin downregulation in retinal pigment epithelial cells. J Agric Food Chem. 2010;58:8246-52.
4. Singh A, Bodakhe SH. Resveratrol delay the cataract formation against naphthalene-induced experimental cataract in the albino rats. J Biochem Mol Toxicol. 2020;34(1):e22420.
5. Smith AJO, Eldred JA, Wormstone IM. Resveratrol inhibits wound healing and lens fibrosis: a putative candidate for posterior capsule opacification prevention. Investig Ophthalmol Vis Sci. 2019;60:3863-77.
6. Doganay S, Borazan M, Iraz M, et al. The effect of resveratrol in experimental cataract model formed by sodium selenite. Curr Eye Research. 2006;31(2):147-53.
7. Oak MH, Bedoui JE, Schini-Kerth VB. Antiangiogenic properties of natural polyphenols from red wine and green tea. J Nutr Biochem. 2005;16(1):1-8.
8. Richer S, Patel S, Sockanathan S, et al. Resveratrol based oral nutritional supplement produces long-term beneficial effects on structure and visual function in human patients. Nutrients. 2014;6(10):4404-20.