RNA Interference Reveals the Coregulatory Effects of Cylindromatosis on Apoptosis and Necroptosis of Photoreceptor Cells in Experimental Retinal Detachment.

Kai Dong, Linfeng Han, Jingwen Liu, Fenghua Wang, Xiaodong Sun

The American journal of pathology 2017 Aug

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Inhibiting only cell apoptosis or necroptosis in photoreceptor cells does not protect them against death after traumatic retinal detachment. This study was designed to evaluate the coregulatory effects of the deubiquitinating enzyme cylindromatosis on the apoptosis and necroptosis of photoreceptor cells in experimental retinal detachment. Lentivirus Cyld shRNA was generated and used to suppress cylindromatosis expression in Sprague-Dawley rats. Three weeks after injection of lentivirus Cyld shRNA, retinal detachment surgery was performed. Transmission electron microscopy, propidium iodide staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, electroretinography, and determination of ubiquitination and phosphorylation of receptor-interacting protein 1 were performed to detect the apoptosis and necroptosis of photoreceptor cells. Knockdown of cylindromatosis expression led to inhibition of caspase 8 activity, a decrease in the number of apoptotic photoreceptor cells, and an increase in the ubiquitination level of receptor-interacting protein 1. In addition, the number of necroptotic cells decreased and the phosphorylation level of receptor-interacting protein 1 decreased dramatically; significant protective effects of RNA interference-mediated suppression of cylindromatosis expression on electroretinogram wave were observed. Cylindromatosis coregulates the apoptosis and necroptosis of photoreceptor cells by regulating the ubiquitination of receptor-interacting protein 1 after retinal detachment. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Citation

Kai Dong, Linfeng Han, Jingwen Liu, Fenghua Wang, Xiaodong Sun. RNA Interference Reveals the Coregulatory Effects of Cylindromatosis on Apoptosis and Necroptosis of Photoreceptor Cells in Experimental Retinal Detachment. The American journal of pathology. 2017 Aug;187(8):1763-1771