Effect of PDGF, IL-1alpha, 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-derived growth factor (PDGF) and PDGF receptors in the human cornea and to study the effects of the PDGF isotypes on proliferation and chemotaxis of human corneal fibroblasts. The effects of interleukin (IL)-1alpha, bone morphogenic protein (BMP)2, and BMP4 on chemotaxis of human corneal fibroblasts were also studied. METHODS mRNA expression was monitored with reverse transcription-polymerase chain reaction (RT-PCR) in primary cultured cells. Protein expression in fresh-frozen human corneal sections was studied with immunocytology. Chemotaxis was measured using a modified Boyden chamber, and proliferation was quantitated 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 cells 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 epithelial basement membrane. PDGF, BMP2, and BMP4 had attractive chemotactic effects on corneal fibroblasts, with the PDGF BB dimer having a significantly greater positive chemotactic effect than the other PDGF isotypes. Interleukin-1alpha had a repulsive chemotactic effect on corneal fibroblasts. PDGF AA, AB, and BB stimulated proliferation of human corneal fibroblasts. CONCLUSIONS The PDGF growth factor receptor system is expressed in the human cornea. PDGF, BMP2, BMP4, and IL-1alpha may modulate keratocyte chemotaxis and proliferation during homeostasis and wound healing.