Rapamycin Inhibited Photoreceptor Necroptosis and Protected the Retina by Activation of Autophagy in Experimental Retinal Detachment

ABSTRACTPurpose: After experimental retinal detachment (RD), the applications of caspase inhibitor z-vad-fmk (a pan-caspase inhibitor) could inhibit apoptosis, but increased receptor interacting protein (RIP)-mediated necroptosis. In this study, we investigated whether rapamycin could inhibit necroptosis and cooperate with z-vad-fmk to protect the retina after RD.Methods: RD animal models were established in Sprague–Dawley rats by subretinal injection of sodium hyaluronate and treated with subretinal injections of z-vad-fmk or z-vad-fmk combined with rapamycin. On day 3 after RD, retinas were collected and analyzed by transmission electron microscopy (TEM), ROS assay, and western blot (for beclin-1, LC-3, RIP-1, AIF). On day 7 after RD, retinas were observed by H&E staining. Vision-dependent behavior of rats was tested by the modified Morris water maze.Results: TEM and H&E staining indicated that rapamycin combined with z-vad-fmk could reduce photoreceptor necrosis and preserve the ONL thickness after RD....