Format

Send to

Choose Destination
Am J Pathol. 2012 Nov;181(5):1634-41. doi: 10.1016/j.ajpath.2012.07.029. Epub 2012 Aug 30.

Necrostatin-1 protects photoreceptors from cell death and improves functional outcome after experimental retinal detachment.

Author information

1
Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, China.

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.

PMID:
22940440
DOI:
10.1016/j.ajpath.2012.07.029
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center