LOCALIZATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND ITS RECEPTORS TO CELLS OF VASCULAR AND AVASCULAR EPIRETINAL MEMBRANES

Aims/background-Epiretinal membranes (ERMs) arise from a variety of ca uses or, in some cases, for unknown reasons. Once established, ERMs te nd to progress, becoming more extensive and exerting increasing tracti on along the inner surface of the retina. One possible cause for their progression is the production of growth factors by cells within ERMs that may provide autocrine or paracrine stimulation. Platelet derived growth factor (PDGF) and its receptors have been localised to cells of ERMs and may play such a role. In this study, comparative data were s ought for several other growth factors that have been implicated in ER M formation. Methods-Immunohistochemical staining of ERMs was done for PDGF-A, PDGF-B, basic fibroblast growth factor (bFGF), three isoforms of transforming growth factor beta (TGF-beta), and vascular endotheli al growth factor (VEGF) and its receptors, flt-1 and flk-1/KDR. Expres sion of flt-1 and flk-1/KDR was examined in cultured retinal pigmented epithelial (RPE) cells and retinal glia from postmortem eyes by immun ohistochemistry and by reverse transcription coupled to polymerase cha in reaction (RT-PCR). Results-Staining was most intense and most frequ ently observed for VEGF and PDGF-A, both in vascular and avascular ERM s. The majority of cells stained for VEGF in nine of 11 (81.8%) diabet ic ERMs and in 14 of 24 (58.3%) proliferative vitreoretinopathy ERMs. The receptors for VEGF, flt-1, and flk-1/KDR were also identified on c ells in ERMs and on cultured RPE cells. By RT-PCR, mRNA for flt-1 was identified in RPE cells and retinal glia, and mRNA for flk-1/KDR was i dentified in RPE cells. Conclusions-These data show that VEGF and its receptors are localised to both vascular and avascular ERMs and sugges t that VEGF, like PDGF-A, may be an autocrine and paracrine stimulator that may contribute to progression of vascular and avascular ERMs.