Endothelial arginase 2 mediates retinal ischemia/reperfusion injury by inducing mitochondrial dysfunction

• DOI: 10.1016/j.molmet.2021.101273
• Publication Date: 2021-06-15T17:46:38Z
• Authors: Esraa Shosha; Abdelrahman Y. Fouda; Tahira Lemtalsi; Stephen Haigh; David Fulton; Ahmed Ibrahim; Mohamed Al-Shabrawey; R. William Caldwell; Ruth B. Caldwell
• Keywords: Mice, Knockout; 0301 basic medicine; Arginase; Endothelial cells; Mice, Transgenic; RC31-1245; Mitochondrial Dynamics; Retina; Mitochondria; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Ischemia; Reperfusion Injury; Animals; Original Article; Internal medicine

Retinal ischemic disease is a major cause of vision loss. Current treatment options are limited to late-stage diseases, and the molecular mechanisms initial insult not fully understood. We have previously shown that deletion mitochondrial arginase isoform, 2 (A2), limits neurovascular injury in models retinopathy. Here, we investigated involvement A2-mediated alterations dynamics function pathology. used wild-type (WT), global A2 knockout (A2KO-) mice, cell-specific mice subjected retinal ischemia/reperfusion (I/R), bovine endothelial cells (BRECs) an oxygen-glucose deprivation/reperfusion (OGD/R) insult. western blotting measure levels cell stress death markers fragmentation protein, dynamin related protein 1 (Drp1). also live labeling Seahorse XF analysis evaluate function, respectively. found I/R-induced disruption layers, fundus abnormalities, albumin extravasation. The specific was protective against neurodegeneration. OGD/R BRECs increased expression induced death, along with decreased respiration, Drp1 expression, fragmentation. overexpression BREC promoted increases Drp1, fragmentation, resulted survival. In contrast, cytosolic (A1), did affect these parameters. This study first show mediates through mechanism involving function.