Eur Rev Med Pharmacol Sci 2020; 24 (9): 4627-4634

DOI: 10.26355/eurrev_202005_21147

Epithelial-mesenchymal transition suppresses ERas to activate autophagy in retinal pigment epithelial cells in proliferative vitreoretinopathy

J. Pan, L.-X. Zhao

Department of Ophthalmology, ZiBo Central Hospital, Zibo City, Shandong, People’s Republic of China. zhaoluxin69@163.com


OBJECTIVE: Proliferative vitreoretinopathy (PVR) is a complex ocular disease that leads to detached retinas and irreversible vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays a critical role in PVR occurrence. However, the core targets driven by the EMT process that lead to the pathogenesis of PVR remain unclear. In our study, the relationship between embryonic stem cell-expressed Ras (ERas) and EMT in RPE cells was investigated.

PATIENTS AND METHODS: The subretinal and epiretinal membrane specimens of human PVR were examined for ERas and hallmarks of autophagy and EMT using Western blotting and immunofluorescence. EMT was induced by transforming growth factor (TGF)-β1 or epidermal growth factor (EGF) in ARPE-19 cells. Autophagy was inhibited by U0126 or bafilomycin A1 in ARPE-19 cells.

RESULTS: ERas was decreased and the classical autophagy biomarker microtubule associated protein 1 light chain 3 alpha (LC3) was upregulated in the subretinal and epiretinal membranes of PVR patients in vivo. Moreover, ERas was downregulated and autophagy was activated in RPE ARPE-19 cells in response to transforming growth factor (TGF)-β1 and epidermal growth factor (EGF) induction. Finally, overexpression of ERas in RPE cells inhibited autophagy via impaired formation of autophagosomes and lysosomes.

CONCLUSIONS: Our study revealed the role of ERas in the pathogenesis of PVR through EMT and provided a novel therapeutic target for PVR prevention and treatment.

Free PDF Download

To cite this article

J. Pan, L.-X. Zhao
Epithelial-mesenchymal transition suppresses ERas to activate autophagy in retinal pigment epithelial cells in proliferative vitreoretinopathy

Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 9
Pages: 4627-4634
DOI: 10.26355/eurrev_202005_21147