Chemoprevention of age-related macular regeneration (AMD) with rapamycin

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among people of 50 year or older. During AMD, vascular endothelial growth factor (VEGF) may become elevated, causing choroidal neovascularization (CNV) and vascular permeability and fragility. Choroidal neovascularization can break in Bruch's membrane, resulting in subretinal hemorrhage, fluid exudation, detachment of the retinal pigment epithelium from the choroid, and formation of fibrotic scars [1]. Patients with neovascular age-related macular degeneration could suffer sudden visual loss due to subretinal hemorrhage or fluid accumulation secondary to choroidal neovascularization. Although neovascular AMD only accounts for less than 15% of the overall age-related macular degeneration, it is responsible for over 80 percent of the severe vision loss cases. Current therapeutics for neovascular AMD are two closely related antibody drugs, ranibizumab (trade name Lucentis) and bevacizumab (trade name Avastin), both of which bind to and neutralize VEGF [2,3]. Bevacizumab is a humanized anti-VEGF monoclonal antibody while ranibizumab is a humanized monoclonal antibody fragment that is made based on the same murine monoclonal antibody as bevacizumab. Ranibizumab is an FDA-approved drug but bevacizumab is used off-label by ophthalmologists. Both agents are used for intravitreal injections, which is cumbersome for patients and is not suitable for preventive treatment. Therefore, new drugs are needed to prevent and treat this type of disease.