Protective Effect And Mechanism Of Polyphenols Against Light-induced Retinal Degeneration

Excessive visible light exposure can induce damage to retinal cells,especially to photoreceptors and retinal pigment epithelial(RPE)cells,and contribute to the development or progression of age-related macular degeneration.Given its high oxygen consumption and high proportion of polyunsaturated fatty acids,the retina is particularly susceptible to light damage and thus is a primary target of photooxidative damage and inflammatory response in the eye.Polyphenols as dietary supplementation exhibited protective effects by scavenging reactive oxygen species(ROS),suppressing oxidative stress and proinflammatory cytokines,and inhibiting retinal cells apoptosis.This study investigated the protective effects of total flavones from H.rhamnoides(TFH)against visible light-induced retinal damage in pigmented rabbits.In addition,we investigated the protective effect of quercetin,cyanidin-3-glucoside(C3G),protocatechuic acid(PCA),ferulic acid(FA)and chlorogenic acid(CA)(0.11 mmol/kg/day)on visible light-induced retinal damage that exhibits retinal cell oxidative stress,inflammation,apoptosis,and angiogenesis,which possesses several pathophysiological characteristics of AMD.In cells that had accumulated A2E and were irradiated with blue light,the protective effect of five polyphenols on photooxidative damage in RPE cells were investigated.We further investigated the protective effect of quercetin and C3G on photooxidation and photodegradation of A2E in RPE cells.The results are as follows:1.The model of visible light-induced retinal damage was established by the pigmented rabbits exposed to light at 18,000 lx for 2 h,and they were sacrificed on day 7 after electroretinogram(ERG)recording,and then performed histological and biochemical analyses.The b-wave amplitudes of ERGs and the ONL thickness of rabbits had decreased at 7 days after light exposure.Retinas from rabbits exposed to visible light showed higher levels of lipid peroxidation,proinflammatory cytokines,angiogenic parameters,and apoptosis.TFH provided functional and structural protection for retinal cells against light-induced retinal degeneration via antioxidant and anti-inflammatory mechanisms.2.The protective effect of quercetin and chlorogenic acid,two polyphenols widely present in edible plant varieties,against light-induced retinal degeneration due to preventing damage from photooxidative stress and alleviating inflammatory responses.Quercetin and CA significantly increased the levels of heme oxygenase-1(HO-1),and quercetin significantly inhibited the expression of nuclear factor kappa B(NF-κB)in retina.3.C3G and its metabolites(PCA and FA)protect the structure and function of photoreceptor cells from light damage.Furthermore,the protective effects of C3G and FA on the scotopic ERG and histological integrity of the retina were more pronounced than that of PCA.C3G and FA play a better role than PCA in reducing the levels of oxidative stress markers(3-nitrotyrosine and 8-OHdG)in the retina.C3G and FA elevated the secretion and expression of nuclear factor erythroid-2 related factor 2(Nrf2)and HO-1.Thus,the protective effects of C3G and FA were mediated,at least in part,by the activation of the Nrf2/HO-1 antioxidant pathway in vivo.C3G,PCA,and FA attenuated the secretion or expression of inflammation-related genes(MCP-1,IL-8 and IL-1β);FA suppressed NF-κB activation.There,FA attenuated the light-induced retinal inflammation by suppressing NF-κB activation.In addition,C3G and its metabolites suppressed the activation of mitochondrial apoptotic pathways.C3G and PCA attenuated the photooxidation-induced angiogenesis(VEGF and HIF-1α)in the retina.4.Quercetin and cyanidin-3-glucoside promoted cell viability and diminished cellular levels of ROS that suppressed ROS adding to carbon-carbon double bonds of A2E thereby inhibiting the photooxidation and photodegradation of A2E.Quercetin and cyanidin-3-glucoside decreased the formation of dicarbonyls methylglyoxal adducts in the RPE cells,and reduced the expression of mRNA encoding receptor for advanced glycation end products.Quercetin and cyanidin-3-glucoside reduced release of the lipid peroxidation product 4-hydroxynonenal in rod outer segments.