Topical dimethyl sulfoxide inhibits corneal neovascularization and stimulates corneal repair in rabbits following acid burn.

Neovascularization of the cornea is characterized by the growth of blood vessels caused by imbalances between angiogenic and anti-angiogenic factors. We investigated whether the expression of Vascular endothelial growth factor (VEGF), Vascular endothelial growth factor receptor (VEGF), Vascular endothelial growth inhibitor (VEGI) receptors, as well as topical drug treatments, participate in regulating corneal neovascularization after corneal damage and remodeling. We used 72 mature male New Zealand rabbits. Corneal burns were induced by hydrofluoric acid under general anesthesia. The rabbits then were treated with indomethacin or dimethyl sulfoxide (DMSO). The animals were euthanized on days 2, 7 and 14 after injury. Each cornea was fixed with 10% neutral formalin. On days 2, 7 and 14, VEGF, flk1/KDR and flt1/fms were strongly expressed in the epithelial, stromal and inflammatory cells, but not in the corneal endothelial cells. On day 7, newly formed blood vessels were observed growing toward the center of the cornea. In the control, indomethacin treated, DMSO-treated, and indomethacin + DMSO-treated animals, VEGI, VEGF, and the receptors, flk1/KDR, flt1/fms and flt4, were expressed at different densities in the neovascular regions. This was particularly evident in the indomethacin- and indomethacin + DMSO-treated groups on days 7 and 14, compared to day 2. Treatment with VEGF and DMSO stimulated repair of corneal damage. We suggest that VEGI in the endothelial cells of neovascularized cornea may act as a signaling protein that promotes balance between cell proliferation and apoptosis. Topical administration of DMSO inhibited corneal neovascularization more effectively than indomethacin.