title: Necrostatin-1 protects photoreceptors from cell death and improves functional outcome after experimental retinal detachment.
abstract: Necroptosis is a recently discovered programmed necrosis. Evidence demonstrated the importance of necroptosis in neuronal cell death. Necrostatin-1 is a specific inhibitor of necroptosis. In this study, we investigated the role of necrostatin-1 on photoreceptor survival and functional protection after experimental retinal detachment (RD) in rats. Necrostatin-1/inactive analogue of necrostatin-1 was introduced into the subretinal space at RD induction and 6 hours afterward, respectively. We found that necrostatin-1 attenuated retinal histopathological damage and reduced plasma membrane breakdown (a morphological hallmark of necroptosis) in outer retinal layers. Transmission electron microscopy showed that necrostatin-1 directly protected neurons by inhibiting necroptotic, not apoptotic, cell death. Treatment with necrostatin-1 inhibited the induction of receptor-interacting protein kinase phosphorylation after RD (a biomarker of necroptosis). Finally, electroretinographic recording proved that necrostatin-1 contributed to objective functional improvement after RD. These findings indicate that necrostatin-1 is a promising therapeutic agent that protects photoreceptors from necroptosis and improves functional outcome.
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dong
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Song
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Gong
authors.forename: Fenghua
authors.initials: F
authors.lastname: Wang
authors.forename: Wenqiu
authors.initials: W
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zheng
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004596:Electroretinography; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D055254:Night Vision / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D011419:Propidium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D012163:Retinal Detachment / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D007093:Imidazoles; D007211:Indoles; C507699:necrostatin-1; D011419:Propidium; D053422:Receptor-Interacting Protein Serine-Threonine Kinases