Abstract
Purpose: :
Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment characterized by re-detachment of the retina as a result of membrane formation and contraction. While the triggers of PVR remain unclear, previous work suggests that a variety of retinal cells, including retinal pigment epithelial (RPE) and Müller cells, as well as the presence of growth factors in the vitreous, may be responsible for this disease. Clinically, patients with large retinal tears allowing RPE cell migration into the vitreous have been found to have an increased risk for the development of PVR. PDGFR has been strongly implicated in the pathogenesis of this disease. PDGFR is found in large quantities in PVR membranes and has found to be intrinsic to the development of PVR in rabbit models. This study explores the expression of PDGFR and PDGFRβ in co-cultures of RPE and Müller cells over time to examine whether these two cell types collaborate in the development of PVR.
Methods: :
Human Müller and ARPE19 cells were grown together in six-well co-culture plates, separated by a trans-well insert with 0.4µm pores. Control groups of a single cell type were grown concurrently. After days 1, 3, 5, and 7, cells were collected and lysates were made. Expression of PDGFR and β in the control and co-culture samples was compared by Western blotting.
Results: :
The expression of PDGFR was up-regulated in experimental Müller and RPE cells by day 5, with a two-fold increase in Müller cells relative to RPE cells. In contrast, the expression of PDGFRβ in Müller cells decreased by day 5 relative to controls. Expression of PDGFRβ remained constant in RPE cells across the seven-day co-culture.
Conclusions: :
These results suggest that Müller and RPE cell interaction in the context of retinal detachment can lead to up-regulation of growth factor receptors, in particular PDGFR, which are responsible for the development of PVR. Our data suggest that Müller cells may play a more active role than previously thought in the development of PVR membranes, particularly when stimulated by an RPE cell-rich environment.
Keywords: proliferative vitreoretinopathy • Muller cells • retinal pigment epithelium