Critical role of SDF-1α-induced progenitor cell recruitment and macrophage VEGF production in the experimental corneal neovascularization

PURPOSE: To address the roles of the stromal derived factor-1 (SDF-1) α in the course of experimental corneal neovascularization (CNV). METHODS: CNV was induced by alkali injury and compared in SDF-1α- or vehicle-treated mice two weeks after injury. Angiogenic factor expression in the early phase after injury was quantified by reverse transcription polymerase chain reaction (RT-PCR). Progenitor cell, macrophage, and monocyte intracorneal accumulation in the early phase after injury was evaluated by flow cytometric analysis. RESULTS: The mRNA expression of SDF-1α was augmented, together with infiltration of c-kit-positive progenitor cells in the corneas after the alkali injury. Compared with vehicle-treated mice, SDF-1α-treated mice exhibited enhanced CNV two weeks after injury, as evidenced by enlarged cluster of differentiation 31 (CD31)-positive areas. Concomitantly, the intracorneal infiltration of c-kit-positive progenitor cells but not F4/80+ macrophages or Ly-6G+ monocytes was significantly enhanced in SDF-1α-treated mice compared to vehicle-treated mice. SDF-1α enhanced vascular endothelial growth factor (VEGF) expression by murine peritoneal macrophages. Enhancement in intraocular VEGF expression was greater in SDF-1α-treated mice than in control mice after injury. Moreover, local administration of C-X-C chemokine receptor type 4 (CXCR4) antagonist after alkali injury reduced alkali-induced CNV. CONCLUSIONS: SDF-1α-treated mice exhibited enhanced alkali-induced CNV through enhanced intracorneal progenitor cell infiltration and increased VEGF expression by macrophages.