Activation of autophagy in photoreceptor necroptosis after experimental retinal detachment
Author:
Corresponding Author:

Affiliation:

(1.Department of Ophthalmology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, Anhui Province, China;2.Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China;3.Eye Research Institute of Shanghi Jiaotong University, Shanghai 200080, China;4.Department of Morphology, Fudan University Shanghai Medical College, Shanghai 200080, China;5.Shanghai Key Laboratory of Fundus Disease, Shanghai 200080, China)

Clc Number:

Fund Project:

Supported by National Basic Research Program of China ‘‘973 Program’’ (No.2011CB707506); Natural Science Foundation of Anhui Province (No.1408085QH159); National Natural Science Foundation of China (No.81170861, 81400407 and 30973259); Shanghai Key Basic Research Foundation (No.11JC141601); Shanghai Scholar Leadship Foundation (No.12XD1404100). Conflicts of Interest: Dong K, None; Zhu ZC, None; Wang FH, None; Ke GJ, None; Yu Z, None; Xu X, None.
ACKNOWLEGEMENTS: The authors thank Wen-Qiu Wang, Qing Gu, Yue Liu, Yue-Qin Tang, Yuan-Yuan Gong (Shanghai First People’s Hospital, School of Medicine, Shanghai Jiaozong University) for their invaluable assistance in this study. We thank Dr. Yang Qin (Menlo Park, California, USA) for help in improving the presentation of this paper. Part of this article’s abstract has been presented on ARVO meeting 2013.

  • Article
  • |
  • Figures
  • |
  • Metrics
  • |
  • Reference
  • |
  • Related
  • |
  • Cited by
  • |
  • Materials
  • |
  • Comments
    Abstract:

    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.

    Reference
    Related
    Cited by
Get Citation

Kai Dong, Zi-Cheng Zhu, Feng-Hua Wang, et al. Activation of autophagy in photoreceptor necroptosis after experimental retinal detachment. Int J Ophthalmol, 2014,7(5):745-752

Copy
Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
Publication History
  • Received:April 01,2014
  • Revised:June 20,2014
  • Adopted:June 20,2014
  • Online: October 20,2014
  • Published: