Decorin, a vitreal proteoglycan, is diminished in patients who develop Proliferative Vitreoretinopathy Retinopathy following retinal detachment

Abstract

Purpose: Transforming Growth Factor (TGF)-β₂ is a key cytokine involved in the development of intraocular scarring after ocular surgery and plays a role in the pathogenesis of Proliferative Vitreoretinopathy (PVR). The intravitreal proteoglycan Decorin has anti-fibrotic activity mediated through antagonism of all isoforms of TGF-β. The aim of this study was to investigate the relationship of TGF-β₂ and Decorin within the eye. We hypothesised that, under normal physiology, Decorin plays a key role in regulating the bioavailability and bioactivity of TGF-β₂, that patients with low levels of Decorin in the vitreous would demonstrate higher levels of vitreal TGF-β₂ and that an increased Decorin:TGF-β₂ ratio may increase the risk of developing PVR after retinal detachment.

Methods: Vitreous samples were collected from patients presenting with rhegmatogenous retinal detachments with and without PVR and macula holes. Patients were excluded if they were under 10 years of age and if they had had previous retinal surgery. During surgery for retinal detachment the vitreous was collected, centrifuged to remove the cell pellet and the supernatant frozen at -80 °C. The supernatant was then analysed by ELISA for the presence of TGF-β₂ and Decorin. ARPE cells were investigated in culture to deduce the interactions between TGF-β₂ and Decorin.

Results: The quantity of intravitreal Decorin was significantly decreased in patients who presented with PVR following retinal attachment surgery to 561±218pg/mL compared to patients with retinal detachment without PVR who demonstrated 1539±226pg/mL. Intravitreal TGF-β₂ levels were increased in patients who presented with PVR following retinal attachment surgery to 8359.61 ± 27 pg/mL compared to patients with retinal detachment without PVR who demonstrated 3174.93±437.2169 pg/mL. In vitro culture of ARPE cells demonstrated that Decorin reversed TGF-β₂ stimulated epithelial-mesenchymal transition ARPE cells, a phenomenon that underlie the development of PVR.

Conclusions: The results indicate that Decorin and TGF-β₂ may be important factors in the development of PVR. Patients who develop PVR have significantly lower levels of Decorin and reciprocally higher levels of TGF-β₂. This link indicates that intravitreal Decorin supplementation in retinal detachment patients may reduce the incidence of PVR.