A stem-cell derived model of geographic atrophy age-related macular degeneration for mitochondrial-focused drug screening
It is now consensus that the cells at the very back of the retina (the retinal pigment epithelial cells or RPE) are compromised in disease. However, the exact mechanisms that cause their death is not well understood. Having access to a patient’s very own retinal cells to study in the laboratory is indeed crucial for understanding how age-related macular degeneration (AMD) and the late-stage dry form of AMD, geographic atrophy (GA) occurs, so that we can screen and develop treatments that prevent or slow progression of the disease. Induced pluripotent stem cells (iPSCs) are a powerful tool to investigate retinal diseases, as cells from patients can be converted into retinal cells to make a patient “biopsy in a dish”. Using iPSCs, we have demonstrated that we can model AMD in the laboratory. Recently, we performed an analysis of patient RPE (iPSC-RPE) using state-of-the-art scientific technology. We found that the energy powerhouses of diseased RPE, the mitochondria, do not function properly and this leads to the cells becoming stressed and functioning less efficiently. In this project, we will extend on this ground-breaking discovery by investigating clinically validated drugs that can rescue the sick mitochondria and assist them to function optimally again, to hopefully find a treatment or cure for AMD.