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Zulma Dueñas, Luz Torner, Ana M. Corbacho, Alejandra Ochoa, Gabriel Gutiérrez–Ospina, Fernando López–Barrera, Fernando A. Barrios, Peter Berger, Gonzalo Martínez de la Escalera, Clapp Carmen; Inhibition of Rat Corneal Angiogenesis by 16-kDa Prolactin and by Endogenous Prolactin-like Molecules. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2498-2505.
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purpose. The cornea is an avascular organ, where induction of new blood vessels
involves the turn-on of proangiogenic factors and/or the turn-off of
antiangiogenic regulators. Prolactin (PRL) fragments of 14 kDa and 16
kDa bind to endothelial cell receptors and inhibit angiogenesis. This
study was designed 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
neovascularization evaluated by the optical density associated with
capillaries stained by the peroxidase reaction and by the number of
vessels growing into the implants. Prolactin receptors in corneal
epithelium were investigated by immunocytochemistry.
results. bFGF induced a dose-dependent stimulation of corneal
neovascularization. This effect was inhibited by coadministration of
16-kDa PRL, as indicated by a 65% reduction in vessel density and a
50% decrement in the incidence of angiogenic responses. Corneal
angiogenic reactions of different intensities were induced by
implantation of polyclonal and monoclonal anti-PRL antibodies. Corneal
epithelial cells were labeled by several anti-PRL receptor monoclonal
conclusions. These findings show that exogenous 16-kDa PRL inhibits bFGF-induced
corneal neovascularization and suggest that PRL-like molecules with
antiangiogenic actions function in the cornea. PRL receptors in the
corneal epithelium may imply that PRL in the cornea derives from
lacrimal PRL internalized through an intracellular pathway. These
observations are consistent with the notion that members of the PRL
family are potential regulators of corneal
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