Choroidal neovascularization (CNV) represents the most common cause of severe vision loss in patients with age-related macular degeneration (AMD). It is also the most common cause of legal blindness in the United States in patients over the age of 60. Therefore, the study of the diagnosis, prevention and treatment of this condition would have a major impact on the public health. We continue to study the pathogenesis and treatment of CNV in an established rodent model of CNV developed in our laboratory. Over the past year, the following has been accomplished:? ? 1. Further study of the role of integrin antagonists in CNV. In a laser ? induced animal model of CNV, the use of C16Y, a 12-mer-integrin antagonist with activity against the ?v?3 and ?5?1 integrin units, demonstrated almost complete suppression of the development of CNV. In addition, intravitreal application of this peptide following the appearance of CNV resulted in the regression of the CNV. Both of these results support th importance of integrin expression in the development of CNV. The results further raise the possibility that anti-integrin therapy may be useful modality for both prevention and treatment of active CNV.? ? 2. Further delineation of the effects of a small molecule integrin antagonist demonstrating a similar anti-angiogenic effect as the C16Y peptide. In-vitro studies have demosntrated that the rate of integrin turnover may be a rate limiting step in integrin antagonist therapy and that sustained exposure to these agents, through the use of sustained delivery steps, may result in increased efficaciousness.
