Resveratrol Ameliorates Retinal Ischemia-Reperfusion Injury by Modulating the NLRP3 Inflammasome and Keap1/Nrf2/HO-1 Signaling Pathway.

Abstract

Glaucoma, as an ischemia-reperfusion (I/R) injury disease, leading irreversible blindness through the loss of retinal ganglion cells (RGCs), mediated by various pathways. Resveratrol (Res) is a polyphenolic compound that exerts protective effects against I/R injury in many tissues. This article aimed to expound the underlying mechanisms through which Res protects RGCs and reduces visual dysfunction in vivo. An experimental glaucoma model was created using 6-8-week wild-type male C57BL/6J mice. Res was injected intraperitoneally for 5 days. The mice were then grouped according to the number of days after surgery and whether Res treatment was administered. We applied the Brn3a-labeled immunofluorescence staining and flash electroretinography (ERG) to assess the survival of RGCs and visual function. The expression of components of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, the interleukin-1-beta (IL-1β), and vital indicators of kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway at the protein and RNA levels were detected respectively. The survival of RGCs was reduced after surgery compared to controls, whereas Res application rescued RGCs and improved visual dysfunction. In conclusion, our results discovered that Res administration showed neuroprotective effects through inhibition of the NLRP3 inflammasome pathway and activation of Keap1/Nrf2/HO-1 pathway. Thus, we further elucidated the potential of Res in glaucoma therapy.