Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions

Ocular angiogenesis may lead to visual impairment and even irreversible blindness in people of all ages worldwide. Choroidal neovascularization (CNV), a major clinical complication of ocular angiogenesis, is an important cause of vision loss that affects a large number of people. Physiological angiogenesis is tightly controlled by a balance in the expression of angiogenic and anti-angiogenic factors. While the underlying mechanism of CNV is complex, it is attributed to an upset in this balance. The vascular endothelial growth factor (VEGF) is essential in the development of CNV as one of the most potent angiogenic stimulators and vascular permeability factors. Pigment epithelium derived factor (PEDF) is a strong inhibitor of angiogenesis with high neuroprotective effects. VEGF and PEDF both possess multiple biological activities and functions that affect a large variety of tissue cells of the eye and other organs. Inappropriate expression levels are associated with many diseases involving neovascularization. This paper describes the unbalanced expressions of VEGF and PEDF as a cause of CNV. Based on the respective angiogenic and anti-angiogenic properties of VEGF and PEDF, experimental models have been devised to genetically reduce VEGF or enhance PEDF to achieve therapeutic effects. Gene therapy for CNV is promising and is under intensive research.