Altered Decorin Biology in Proliferative Vitreoretinopathy: A Mechanistic and Cohort Study

PURPOSE. To determine if vitreous levels of the pro-fibrotic cytokine transforming growth factor beta2 (TGF beta 2) and its opposing regulator decorin predict subsequent proliferative vitreoretinopathy (PVR) development in patients with rhegmatogenous retinal detachment (RRD). METHODS. WC examined the effect of TGE-beta 2 and decorin n epithelial-mesenchymal transition (EMT) and collagen expression in vitro using ARPE-19 cells, and we analyzed extracellular matrix marker expression in PVR membrane and internal limiting membrane patient samples. We performed a prospective noninterventional cohort study, recruiting 125 patients undergoing vitrectomy for RRD and macular hole surgery measured vitreous levels of TGE beta 2 and decorin by ELISA, and followed them up for 6 months. Patients who did not develop PVR were compared to those who did, in order to determine whether vitreous TGF-beta 2 and decorin levels predicted PVR development. RESULTS. In vitro, TGF beta 2 induced. EMT and collagen production. Decorin strongly inhibited. EMT and collagen production at high levels. PVR membranes expressed high levels of fibrosis associated proteins, consistent with EMT Vitreous TGE-beta 2 levels were unchanged between patients with macular holes and RRD who did or did not subsequently develop PVR. Average decorin levels were higher in the vitreous of RRD patients who subsequently developed PVR compared to those who did not, but at the measured vitreous concentrations (1-2 ug/mL), decorin did not demonstrate an in vitro inhibitory effect on EMT. CONCLUSION. In vitro, high concentrations of decorin inhibited EMT and fibrosis. At he levels seen in human vitreous, decorin did not prevent fibrosis or EMT in vitro, and higher initial vitreous decorin levels were associated with the development of postoperative PVR after vitrectomy to treat RRD, but did not reliably predict the outcome.