Mice deficient in the Vici syndrome gene Epg5 exhibit features of retinitis pigmentosa

• Published in: Autophagy Vol. 12; no. 12; pp. 2263 - 2270
• Main Authors: Miao, Guangyan, Zhao, Yan G., Zhao, Hongyu, Ji, Cuicui, Sun, Huayu, Chen, Yingyu, Zhang, Hong
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.12.2016
• Subjects: Agenesis of Corpus Callosum - genetics; Agenesis of Corpus Callosum - physiopathology; Animals; Apoptosis; Autophagy; Basic Brief Report; Cataract - genetics; Cataract - physiopathology; Mice, Inbred C57BL; Mice, Knockout; Photoreceptor Cells, Vertebrate - metabolism; Photoreceptor Cells, Vertebrate - pathology; Proteins - genetics; Proteins - metabolism; Retina - pathology; Retina - physiopathology; Retinal Degeneration - complications; Retinal Degeneration - pathology; Retinal Degeneration - physiopathology; Retinitis Pigmentosa - complications; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - pathology; Retinitis Pigmentosa - physiopathology; Unfolded Protein Response; Epg5; neurodegeneration; retinitis pigmentosa; autophagy; UPR
• ISSN: 1554-8627; 1554-8635; 1554-8635
• DOI: 10.1080/15548627.2016.1238554

Autophagy helps to maintain cellular homeostasis by removing misfolded proteins and damaged organelles, and generally acts as a cytoprotective mechanism for neuronal survival. Here we showed that mice deficient in the Vici syndrome gene Epg5, which is required for autophagosome maturation, show accumulation of ubiquitin-positive inclusions and SQSTM1 aggregates in various retinal cell types. In epg5 retinas, photoreceptor function is greatly impaired, and degenerative features including progressively reduced numbers of photoreceptor cells and increased numbers of apoptotic cells in the outer nuclear layer are observed, while the morphology of other parts of the retina is not severely affected. Downstream targets of the unfolded protein response (UPR), including the death inducer DDIT3/CHOP, and also levels of cleaved CASP3 (caspase 3), are elevated in epg5 retinas. Thus, apoptotic photoreceptor cell death in epg5 retinas may result from the elevated UPR. Our results reveal that Epg5-deficient mice recapitulate key characteristics of retinitis pigmentosa and thus may provide a valuable model for investigating the molecular mechanism of photoreceptor degeneration.