NEW INHIBITORS OF VEGF-DEPENDENT ANGIOGENESIS ASSOCIATED TO OCULAR NEOVASCULAR DISEASES

The growth of new vessels, know as angiogenesis, is one of the major pathological changes associated with several complex diseases. Among them, the ocular neovascularization in diseases as diabetic retinopathy and age-related macular degeneration (AMD), are of great clinical relevance since are responsible for the most cases of irreversible blindness. AMD is a genetic disease responsible for 75% of blindness in the population of age 50 years old or older in developed countries. Two types of AMD are known: the atrophic or dry form, characterized by deposition of drusen, a complex deposits of lipids, protein and inflammatory mediators, and wet or exudative form, characterized by choroid neovascularization (CNV) and sub-retinal pigment epithelium (RPE) or sub-retinal hemorrhage. Although the atrophic form accounts for 80% of diagnosed cases, the wet form that develop CNV accounts for 80-90% of the vision loss in AMD patients. The involvement of vascular endothelial growth factor (VEGF), the most potent factor know able to stimulate the growth of new vessels, in promoting CNV has been clearly documented in patients and in animal experimental models. Consequently, the inhibition of CNV stimulated by VEGF has represented, in the last years, one of the main targets for new therapeutic approach aimed to block CNV in AMD patients. The objective of this project is to explore the efficacy of new inhibitors of the VEGF activity in AMD experimental models, following two approaches: gene therapy, using a gene which ability to inhibit VEGF activity has already been demonstrated in experimental tumor models, and the use of small molecules able to neutralize the interaction of VEGF family members with VEGF receptors, the initial and crucial molecular event for VEGF family members activity. The obtained result possibly will represent an advance in scientific research toward therapeutic approach for AMD.