Effect of PDGF, IL-1 alpha, and BMP2/4 on corneal fibroblast chemotaxis: Expression of the platelet-derived growth factor system in the cornea

PURPOSE. The purpose of this study was to examine expression of platelet-de rived growth factor (PDGF) and PDGF receptors in the human cornea and to st udy the effects of the PDGF isotypes on proliferation and chemotaxis of hum an corneal fibroblasts. The effects of interleukin (IL)-1 alpha, bone morph ogenic protein (BMP)2, and BMP4 on chemotaxis of human corneal fibroblasts were also studied. METHODS. mRNA expression was monitored with reverse transcription-polymeras e chain reaction (RT-PCR) in primary cultured cells. Protein expression in fresh-frozen human corneal sections was studied with immunocytology. Chemot axis was measured using a modified Boyden chamber, and proliferation was qu antitated by cell counting. RESULTS. PDGF A, PDGF B, PDGF receptor alpha, and PDGF receptor beta mRNAs were detected in corneal epithelial cells, fibroblasts, and endothelial cel ls in culture. The proteins were expressed in each major cell type in human corneal sections, with PDGF A and PDGF B detected at high levels in the ep ithelial basement membrane. PDGF, BMP2, and BMP4 had attractive chemotactic effects on corneal fibroblasts, with the PDGF BE dimer having a significan tly greater positive chemotactic effect than the other PDGF isotypes. Inter leukin-la had a repulsive chemotactic effect on corneal fibroblasts. PDGF A A, AB, and BE stimulated proliferation of human corneal fibroblasts. CONCLUSIONS. The PDGF growth factor receptor system is expressed in the hum an cornea. PDGF, BMP2, BMP4, and IL-1 alpha may modulate keratocyte chemota xis and proliferation during homeostasis and wound healing.