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Abstract #95084 Published in IGR 22-2

Resveratrol attenuates retinal ganglion cell loss in a mouse model of retinal ischemia reperfusion injury via multiple pathways

Ji K; Li Z; Lei Y; Xu W; Ouyang L; He T; Xing Y
Experimental Eye Research 2021; 209: 108683


BACKGROUND: Resveratrol (RES) is a natural polyphenol that has been shown to protect retinal ganglion cells (RGCs) following retinal ischemia reperfusion (I/R) injury. However, the molecular mechanisms of resveratrol function are yet to be fully elucidated. Thus, this study explored the potential mechanisms of resveratrol in vivo. METHODS: A retinal ischemia reperfusion injury model was established in adult male C57BL/6 J mice. Intraperitoneal injection of resveratrol was administered continuously for 5 days. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function. Proteins of HIF-1a, VEGF, p38, p53, PI3K, Akt, Bax, Bcl2, and Cleaved Caspase3 were detected using Western blot. RESULTS: RES administration significantly ameliorated retinal thickness damage and increased Brn3a stained RGCs 7 days after I/R injury. We also found that administration of RES remarkably inhibited the upregulation of mitochondrial apoptosis-related protein Bax and Cleaved Caspase3, as well as increased the expression of Bcl2. Furthermore, RES administration significantly suppressed the I/R injury-induced upregulation of the HIF-1a/VEGF and p38/p53 pathways, while activating the I/R injury-induced downregulation of the PI3K/Akt pathway. Moreover, RES administration remarkably improved retinal function after I/R injury-induced functional impairment. CONCLUSIONS: Our data demonstrated that resveratrol can mitigate retinal ischemic injury induced RGC loss and retinal function impairment by inhibiting the HIF-1a/VEGF and p38/p53 pathways while activating the PI3K/Akt pathway. Therefore, our results further reinforce that resveratrol has potential for treating glaucoma.

Department of Ophthalmology, Renmin Hospital of Wuhan University, Hubei, China.

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