Cell cycle re-entry and arrest in G2/M phase induces senescence and fibrosis in Fuchs Endothelial Corneal Dystrophy.

In this study, we have provided further insights into the pathogenesis of the disease, showing a causal relationship between senescence and endothelial-mesenchymal transition (EMT) using in vitro and in vivo models. Ultraviolet A (UVA) light induced EMT and senescence in CEnCs. Senescent cells were arrested in G2/M phase of the cell cycle and responsible for the resulting profibrotic phenotype. Inhibiting ATR signaling and subsequently preventing G2/M arrest attenuated EMT. In vivo, UVA irradiation induced cell cycle re-entry in post mitotic CEnCs, resulting in senescence and fibrosis at 1- and 2-weeks post-UVA. Selectively eliminating senescent cells using the senolytic cocktail of dasatinib and quercetin attenuated UVA induced fibrosis, highlighting the potential for a new therapeutic intervention for FECD. PMID: 33418109 [PubMed - as supplied by publisher]

https://www.ncbi.nlm.nih.gov/pubmed/33418109?dopt=Abstract

Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: White TL, Deshpande N, Kumar V, Gauthier AG, Jurkunas UV Tags: Free Radic Biol Med Source Type: research