Ucf-101 alleviates Ischaemia/Reperfusion induced retinal inflammation and injury via suppressing oxidative damage

Abstract

The Omi/HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryliodine]-1,3-diphenyl-2-thiobarbituric acid (Ucf-101) has shown neuroprotective effects in the central nervous system. However, whether Ucf-101 can protect retinal ganglion cells (RGCs) after retinal ischemia/reperfusion (IR) has not been investigated. We aimed to investigate the effects of Ucf-101 on RGCs apoptosis and inflammation after IR-induced retinal injury in mice. We injected Ucf-101 into the mouse vitreous body immediately after IR injury. After 7 days, hematoxylin and eosin staining was conducted to assess retinal tissue damage. Next, retrograde labeling with FluoroGold, counting of RGCs and TUNEL staining were conducted to evaluate apoptosis. Immunohistochemistry, immunofluorescence staining, and western blotting were conducted to analyze protein levels. IR injury-induced retinal tissue damage could be prevented by Ucf-101 treatment. The number of TUNEL-positive RGCs was reduced by Ucf-101 treatment in mice with IR injury. Ucf-101 treatment inhibited the upregulation of Bax, cleaved caspase-3 and cleaved caspase-9 and activated the JNK/ERK/P38 signaling pathway. Furthermore, Ucf-101 treatment inhibited the upregulation of glial fibrillary acidic protein (GFAP), vimentin, Iba1 and CD68 in mice with IR injury. Ucf-101 prevents retinal tissue damage, improves the survival of RGCs, and suppresses microglial overactivation after IR injury. Ucf-101 might be a potential target to prevent RGCs apoptosis and inflammation in neurodegenerative eye diseases.

Keywords: Apoptosis; Inflammation; Reactive microglia; Retinal ganglion cells; Retinal ischemia/reperfusion; Ucf-101.