Calpain inhibitors reduce retinal hypoxia in ischemic retinopathy by improving neovascular architecture and functional perfusion

►Hypoxia activates calpain in retinal endothelial cells. ►Calpain inhibitors, at suitable doses, improve the architecture of hypoxia-induced retinal neovessels. ►With optimal doses of calpain inhibitors, retinal neovessels exhibit reduced leakiness. ►Improved retinal neovascularization results in reduced retinal hypoxia. ►Optimal administration of calpain inhibitors likely improves neovessel architecture by stabilizing actin.