Transforming growth factor beta 2 as a biomarker for detection of disease progression of proliferative vitreoretinopathy

Abstract

Purpose : Proliferative vitreoretinopathy (PVR) is a debilitating disease which affects 5-10% of patients with retinal detachment. PVR development is in part caused by epithelial mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE). Transforming growth factor beta 2 (TGFB2) promotes RPE EMT. We hypothesised that vitreous TGFB2 levels would predict and cause the development of PVR, modulated by Decorin and that in vitro; Decorin would sequester TGF-beta and prevent EMT in human RPE cells.

Methods : We collected Vitreous from patients undergoing vitrectomy for retinal detachment or macular holes. Levels of TGFB2 and Decorin were measured by TGFB2 and Decorin ELISA. Data was compared to PVR development. To assess the effects of Decorin and TGFB2 on EMT, human ARPE-19 cells were treated with TGFB2 and different concentrations of Decorin. Markers of EMT and fibrosis were assessed by qPCR.

Results : Vitreous TGFB2 levels, were similar between patients presenting with macular holes, retinal detachment, those that went onto develop PVR and those that initially presented with PVR. Patients who subsequently developed PVR had a trend towards increased Decorin expression compared to those that initially presented with retinal detachment. Treatment of ARPE-19 cells with TGFB2 had increased Alpha-SMA (p<0.01), Collagen type 1 (p<0.01) and Fibronectin expression (p<0.05). Addition of increasing concentrations of Decorin caused decreased Alpha-SMA (p<0.05), Collagen type 1 (p<0.05), Vimentin (p<0.005)and Fibronectin (p<0.05) mRNA expression.

Conclusions : TGFB2 levels in the vitreous at the time of vitrectomy are not associated with PVR disease progression. TGFB2 treatment in human RPE cells causes EMT. Decorin reduces EMT in a dose-dependent fashion and could therefore provide a potential therapeutic strategy to block EMT inducing factors, preventing RPE EMT and subsequent fibrosis characteristic of PVR.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.