Stage Specificity of Novel Growth Factor Expression During Development of Proliferative Vitreoretinopathy

Abstract

Abstract: : Purpose: To compare the relative levels of connective tissue growth factor (CTGF), platelet derived growth factor alpha (PDGF–AA) and hepatocyte growth factor (HGF) in glial and retinal pigment epithelial (RPE) cells of epiretinal membranes from proliferative vitreoretinopathy (PVR). Methods: Thirty–seven PVR membranes, at various stages of PVR, were collected from eyes via vitreoretinal surgery. The membranes were set in an OCT compound mold and stored at –80°C. The membranes were sequentially cut into 6µm sections. A double immunohistochemical staining procedure was used to identify the presence of growth factors and specific cell types. The tissue sections underwent fluorescent immunohistochemisty and confocal laser scanning microscopy to localize CTGF, HGF and PDGF–AA in RPE and glial cells. Results: Numerous RPE, and relatively fewer glial cells, were found in all stages of PVR. CTGF was present in high concentration throughout PVR development, and was principally expressed by RPE cells in early stage, and by glial cells in late stage, PVR. HGF, expressed by both RPE and glial cells, was principally expressed in mid–stage PVR. PDGF–AA, expressed by both cell types, demonstrated a uniform level of staining throughout all stages of PVR. Conclusions: RPE and glial cells contribute to the expression of CTGF, HGF, and PDGF–AA during PVR, but with specific developmental patterns. PDGF–AA is expressed uniform throughout all stages of PVR, while HGF expression peaks during mid stage, and CTGF expression is highest during late stage PVR. These results allow for the development of stage–specific therapeutics for PVR that may allow targeting of the proliferative or the tractional stages of PVR.

Keywords: proliferative vitreoretinopathy • growth factors/growth factor receptors • immunohistochemistry