Ernesto Moreira, M.D.
SUMMARY OF LABORATORY RESEARCH
Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 60 and will become more of a health problem with aging of our population. Therefore, there is a pressing need to find a therapeutic solution for this devastating disease. Current treatment options for AMD include (although not limited to) surgery, thermal laser photocoagulation, photodynamic therapy and anti-VEGF therapy (Del Priore LV, et al. 2006). Although these therapeutic alternatives are effective in delaying the progression of the wet form of AMD, they do not provide a comprehensive treatment for patients with geographic atrophy (GA) in advanced stages of AMD.
During the pathogenesis of AMD there is extensive loss of the retinal pigment epithelium (RPE) early in this disease. There is evidence that damage to the RPE happens, at least in part, due to age-related changes in the Bruch’s membrane, a thin penta-laminar structure to which the RPE is attached and indispensable for its survival. Photoreceptor degeneration, and vision loss, is the last step of the AMD disease mechanism, and it begins after the RPE function has been compromised. Thus, our ultimate goal is to provide an alternative treatment and more permanent solution for AMD patients in the form of RPE/Bruch’s membrane transplantation. At this time the goal of my research is to perform experiments in vitro, using human RPE cells (ARPE19 cells) and human induced pluripotent stem cells (hiPSC)-derived RPE to study the effects of aging Bruch’s membrane (BM) on RPE cell functions. BM is composed of extra-cellular membrane (ECM) proteins, such as laminin, fibornectin and collagen type IV that mediate attachment between the RPE and BM. Previously, our laboratory has shown that aging of the BM affects the attachment rate, survival, and gene profile expression of the overlying monolayer of cultured RPE cells (Sun K. et al, 2007). These observed effects are attributed to age-related changes within the BM, such as collagen cross-linking, elastin fragmentation and deposition of abnormal material (Del Priore LV, et al. 2006). Current experiments are aimed at investigating the effects of age and/or diseased related changes of human BM on the phagocytosis rate of RPE cells (immortalize and hiPSC-derived RPE). We are also developing techniques that can be used in vivo to reengineer aged or diseased BM to make this surface a good substrate for attachment and proliferation of transplanted RPE cells. These experiments will provide a knowledge platform to be able to better reconstruct the RPE/BM needed for transplantation in patients with AMD.