• Kai Dong, Hong Zhu, Zhengyu Song, Yuanyuan Gong, Fenghua Wang, Wenqiu Wang, Zhi Zheng, Zhang Yu, Qing Gu, Xun Xu, and Xiaodong Sun.
• Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, China.
• Am. J. Pathol. 2012 Nov 1; 181 (5): 1634-41.

AbstractNecroptosis 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.Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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