Inhibition of rat corneal angiogenesis by 16-kDa prolactin and by endogenous prolactin-like molecules

PURPOSE. The cornea is an avascular organ, where induction of new blood ves sels involves the turn-on of proangiogenic factors and/or the rum-off of an tiangiogenic regulators. Prolactin (PRL) fragments of 14 kDa and IG kDa bin d to endothelial cell receptors and inhibit angiogenesis. This study was de signed to determine whether antiangiogenic PRL-like molecules are involved in cornea avascularity. METHODS. Sixteen-kDa PRL and basic fibroblast growth factor (bFGF) or anti- PRL antibodies were placed into rat cornea micropockets and neovascularizat ion evaluated by the optical density associated with capillaries stained by the peroxidase reaction and by the number of vessels growing into the impl ants. Prolactin receptors in corneal epithelium were investigated by immuno cytochemistry. RESULTS. bFGF induced a dose-dependent stimulation of corneal neovasculariz ation. This effect was inhibited by coadministration of 16-kDa PRL, as indi cated by a 65% reduction in vessel density and a 50% decrement in the incid ence of angiogenic responses. Corneal angiogenic reactions of different int ensities were induced by implantation of polyclonal and monoclonal anti-PRL antibodies. Corneal epithelial cells were labeled by several anti-PRL rece ptor monoclonal antibodies. CONCLUSIONS. These findings show that exogenous 16-kDa PRL inhibits bFGF-in duced corneal neovascularization and suggest that PRL-like molecules with a ntiangiogenic actions function in the cornea. PRL receptors in the corneal epithelium map imply that PRL in the cornea derives from lacrimal PRL inter nalized through an intracellular pathway. These observations are consistent with the notion that members of the PRL family are potential regulators of corneal angiogenesis.