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

Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2498-505.


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 antibodies.

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 angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Blotting, Western
  • Cornea / blood supply
  • Cornea / drug effects*
  • Corneal Neovascularization / chemically induced
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / prevention & control*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium, Corneal / metabolism
  • Fibroblast Growth Factor 2 / antagonists & inhibitors
  • Fibroblast Growth Factor 2 / pharmacology
  • Immunoenzyme Techniques
  • Male
  • Molecular Weight
  • Peptide Fragments
  • Prolactin / immunology
  • Prolactin / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Prolactin / metabolism


  • Antibodies, Monoclonal
  • Peptide Fragments
  • Receptors, Prolactin
  • Fibroblast Growth Factor 2
  • Prolactin