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摘要
AIM: To investigate whether photoreceptor necroptosis induced by z -VAD -FMK (pan caspase inhibitor) was involved the activation of autophagy and whether Necrostatin -1, a specific necroptosis inhibitor, could inhibit this induction of autophagy after experimental retinal detachment. @@@ METHODS: Experimental retinal detachment models were created in Sprague -Dawley rats by subretinal injection of sodium hyaluronate and subretinal injections of z-VAD-FMK, vehicle or z-VAD-FMK plus Necrostatin-1. Three days after retinal detachment, morphologic changes were observed by transmission electron microscopy. In other animals, retinas were subjected to immunoprecipitation and Western Blotting, then probed with anti -RIP1, phosphoserine, LC -3II or caspase 8 antibody. @@@ RESULTS: It was proved by immunoprecipitation and western blotting, that photoreceptor necroptosis was mediated by caspase -8 inhibition and receptor interacting protein kinase (RIP1) phosphorylation activation., Transmission electron microscope and western blotting results indicated that photoreceptor necroptosis was involved the LC -3II and autophagosomes induction. We also discovered Necrostatin -1 could inhibit RIP1 phosphorylation and LC-3II induction. @@@ CONCLUSION: These data firstly indicate photoreceptor necroptosis is associated with the activation of autophagy. Necrostatin -1 protects photoreceptors from necroptosis and autophagy by down -regulation of RIP1 phosphorylation and LC-3II.
