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C.N. Nagineni, V. Kutty, B. Detrick, J.J. Hooks; Expression of PGDF Isoforms and their Receptors in Human RPE and Choroid Fibroblasts: Regulation by TGF- ß . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2956.
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Purpose: Platelet derived growth factor (PDGF) is known to be associated with a variety of ocular proliferaive and angiogenic disorders by promoting proliferation and migration of fibroblasts, smooth muscle, glial and retinal pigment epithelial (RPE) cells. Expression of PDGF isoforms and the effect of PDGF were studied in human RPE cells (HRPE) and choroid fibroblasts (HCHF). Methods: HRPE and HCHF cultures were prepared from human donor eyes. The cultures were incubated in serum free media in the presence of various cytokines and growth factors.The concentrations of three isoforms of PDGF (AA, AB, BB) in culture supernatants were determined by ELISA. Expression of PDGF-A, PDGF-B, PDGF receptor-α and PDGF receptor-ß mRNA was analyzed by RT-PCR. The effect of three PDGF isoform proteins on cell proliferation was measured by cell proliferation assay (CellTiter 96). Results: Unstimulated HRPE cultures secreted PDGF-AA (23 pg/ml) and PDGF-AB (530 pg/ml) and this secretion was enhanced by TGF-ß to 480 pg/ml and 3600 pg/ml respectively. Other growth factors and cytokines studied had no significant effects. PDGF-BB secretion was not detected in control and TGF-ß treated HRPE. In contrast, HCHF cultures did not secrete all three PDGF isoforms under any of these conditions. Expression of PDGF-A subunit and PDGF-B subunit mRNA was observed in untreated HRPE and both were up regulated by TGF-ß. PDGF receptor-α and PDGF receptor-ß mRNA expression was observed predominantly in HRPE and HCHF respectively. TGF-ß and other agents tested had no effect on PDGF receptor expression. All three human rPDGF isoforms significantly enhanced proliferation of HCHF cells but had no effects on HRPE. Conclusions: TGF-ß enhanced the secretion of PDGF-AB and AA by HRPE. This secreted PDGF may induce proliferation and migration of choroidal and retinal cells into subretinal space or into vitreous, augmenting proliferative vitreo-retinal disorders.
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