Modulation of corneal vascularization

Avascularity of normal cornea is a result of homeostasis between anti-angiogenic and pro-angiogenic stimuli. Disruption of this delicate balance during corneal wound healing can lead to pathological corneal vascularization. Several unique characteristics in the ocular surface epithelia modulate corneal avascularity. Normal cornea contains heparan sulfate to prevent the release of potent angiogenic cytokines, such as basic fibroblast growth factor (bFGF) from the Bowman's layer. Potent angiostatic factors, such as endostatin and angiostatin, can be produced from degradation of corneal extracelluar matrix. In contrast, conjunctiva contains angiogenic cytokines, such as bFGF and vascular endothelial growth factor. In addition to regulating release of angiogenic and angiostatic cytokines, matrix metalloproteinases (MMPs) and other proteolytic enzymes can modulate corneal vascularization via matrix degradation to allow endothelial migration and tissue remodeling. When the cornea becomes vascularized, inflammatory cells and mediators gain uninhibited access to the cornea, thus rendering immune sensitization and increased risk of corneal graft rejection. Novel therapies targeting angiogenic cytokines or MMPs have been shown to suppress corneal vascularization effectively in animal models, and may have therapeutic potential for clinical use.