[Molecular mechanism for choroidal neovascularization in age-related macular degeneration]

Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) is the most common cause of severe visual loss in patients over age 60 years in developed countries. While much is unknown about the underlying pathogenesis of CNV, the increased production of vascular endothelial growth factor(VEGF) by retinal pigment epithelium (RPE) is thought to play a central role in the development of this condition. However, recent studies using gene-manipulated mice question the importance of VEGF alone in promoting CNV. Angiogenesis is thought to result from the balance between angiogenesis stimulation and inhibition. A potent antiangiogenic factor recently has been identified in the retina and shown to be secreted by RPE cells. The inhibitor, pigment epithelium-derived factor(PEDF) is considered the key factor associated with avascularity of the cornea, vitreous, and outer retinal layer of the eye. We recently demonstrated that an imbalance between PEDF and VEGF in RPE cells caused by aging and oxidative stress may contribute to the disregulation of endothelial cell proliferation in CNV. In this review, we also discuss the angiogenic role of inflammatory cells in CNV, age-related changes in Bruch's membrane, and the possibility of the development of animal models reflecting CNV in AMD.