Understanding the role of autophagy in the pathogenesis of AMD using a patient specific iPSC model (360G-Wellcome-206830_Z_17_Z)

AMD remains the most important cause of blindness in the elderly. The number of AMD affected people in UK is expected to rise to 1.3 M by 2050 with healthcare costs rising to £16.4 billion during 2010-2020. Currently there is no effective treatment hence a huge unmet need for investigations into therapies. This project aims to contribute to the identification of the underlying causes of AMD by interrogating a new cell model created by the host lab. Preliminary data suggest that autophagy, a process by which the cells remove waste products, is impaired in retinal pigmented epithelial cells derived from patients with AMD, leading to deposition of waste products and increased stress. Using this model, I will investigate which step of the autophagic process is not functioning properly in retinal cells, thus leading to a better understanding of AMD etiology. To date, small molecules that regulate autophagy are used in clinical trials of other neurodegenerative diseases. By the end of this project we will find out if the existing small molecules restore the autophagy in retinal cells of AMD patients. This will contribute to the design of preclinical studies for preventing further progression of AMD and restoring sight loss.