Seeing the light: new insights into the molecular pathogenesis of retinal diseases

In the past, most treatments for retinal diseases have been empirical. Steroids and/or laser photocoagulation and/or surgery have been tried for almost every condition with little or no understanding of the underlying disease. Over the past several years vision researchers have uncovered molecular components of processes, such as visual transduction and the visual cycle, that are critical for visual function, and identified other molecules that lead to dysfunction and disease processes such as neovascularization and macular edema. It is becoming clear that dysregulation of certain molecules can have major effects on retinal structure and function. Studies in animal models have suggested that inhibiting or augmenting levels of a single molecule can have major effects in complex disease processes. Although several molecules probably contribute to neovascularization and excessive vascular permeability in the eye, blockade of vascular endothelial growth factor (VEGF) has remarkable beneficial effects in animal models that have now been proven to apply to human diseases in clinical trials. Intraocular injection of VEGF antagonists has revolutionized the treatment of choroidal neovascularization (CNV) and macular edema and serves as a model of targeted ocular pharmacotherapy. Significant progress elucidating the molecular pathogenesis of several disease processes in the eye may soon lead to new treatments following the lead of VEGF antagonists. Initial treatments that provide benefit from frequent intraocular injections are likely to be followed by sustained delivery of drugs and/or prolonged protein delivery by gene transfer. The eye has entered the era of molecular therapy.