Suppression of Light-Induced Retinal Degeneration by Quercetin via the AP-1 Pathway in Rats

Abstract

We examined the cytoprotective effect of quercetin via activator protein (AP-1) and the heat shock protein 70 (Hsp70) pathway against light-induced retinal degeneration in rats. Quercetin was administered intraperitoneally to Sprague-Dawley rats for seven days before light exposure to intense white fluorescent light (3000 lux) for 24 h. Light-induced retinal damage was determined by the number of rows of photoreceptor cell nuclei, the microstructures of the rod outer segments and retinal pigment epithelium, and terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine-5'-triphosphate (dUTP) nick end labeling. To elucidate the cytoprotective mechanism of quercetin, expression levels were measured in the rat retinas of 8-hydroxy-deoxyguanosine (8-OHdG), a marker of oxidative stress; Hsp70; and transcription factor AP-1 transcription activity. Pretreatment with quercetin inhibited light-induced photoreceptor cellular apoptosis and subsequent retinal degeneration in rats. 8-OHdG and Hsp70 protein expressions were up-regulated markedly by light exposure and suppressed by quercetin pretreatment. The results of an electrophoretic mobility shift assay showed that AP-1-binding activity was activated by light exposure, and binding of c-Fos and c-Jun, but not JunB, mediated the binding activity. Intraperitoneal administration of quercetin decreases photooxidative damage in the retina and mediates cytoprotection against light-induced photoreceptor cell degeneration in rats. Suppression of the heterodimeric combination of c-Jun and c-Fos proteins at the AP-1 binding site is highly involved in quercetin-mediated cytoprotection.

The potential health benefits of dietary natural plant products in age related eye diseases

“…(2010) in their different experiments observed that 50 μM of quercetin protected human RPE cells from oxidative stress, cellular senescence and also inhibited pro-inflammatory molecules, which resulted in the prevention of age-related macular degeneration (AMD). Koyama et al. (2019) reported that 50 mg/bodyweight/kg of quercetin in rat model experiment decreased photooxidative damage in the rat retina.…”

“… Inhibits age-related eye diseases. Koyama et al. (2019) Quercetin 50 mg/kg/day Diabetic rat retina Protects the neuronal damage, ameliorates neurotrophic factors and inhibits the apoptosis of neurons Prevents neurodegeneration in diabetic retinopathy.…”

Food Supplements in the Treatment of Ophthalmic Diseases: Preclinical and Clinical Studies

“…In a different model of peroxide-induced oxidative stress model in RPE cells [409] quercetin treatment influenced the transcription of genes involved in apoptosis regulation, including the anti-apoptotic Bcl-2 and the proapoptotic BAX and FADD, and the effectors of apoptosis Caspase-3 and Caspase-9. Intraperitoneal administration of quercetin blunted the photo-oxidative damage of rat retinas' photoreceptors exposed to intense light [410]. Curcumin, a polyphenol from Curcuma longa (turmeric plant) belonging to the ginger family, is also able to modulate apoptosis, inflammation and oxidative stress defense proteins [411]; these effects follow the upregulation of the anti-apoptotic protein Bcl-2, the downregulation of the pro-inflammatory transcription factor NF-kB, and the upregulation of the antioxidant proteins SOD, GR and HO-1, as shown in human retinal cell models exposed to oxidative damage [350,412].…”

Mitochondrial Dysfunction as a Novel Target for Neuroprotective Nutraceuticals in Ocular Diseases

“…On the other hand, some studies have demonstrated that quercetin has an inhibitory effect of heat shock protein 72 (HSP 72) in RGCs [ 95 , 96 , 97 ]. Quercetin has neuroprotective effects of retinal layers [ 98 ] and cytoprotective effects of photoreceptor, RPE and RGCs through inhibiting activity of AP-1 pathway [ 99 ] in light-induced retinal degeneration rodent models. It attenuates hyperglycemia [ 100 ] and dyslipidemia [ 101 ], and also has anti-retinal oxidative stress, anti-neuroinflammation and anti-apoptosis protective effects in diabetic animal models [ 102 ].…”