The Relationship Between Genetic Predisposition and Age in AMD

Age-related macular degeneration (AMD) affects more than 2 million individuals in the US and it will reach 3 million by 2020. Current therapies can improve vision only in some patients with advanced AMD; unfortunately, there is no effective therapy that prevents disease progression in patients with early disease or genetic predisposition. My aim is to create a cell-based model to discover the primary mechanisms activated by the combination of aging and genetic variants in complement genes in patients with early AMD; so that drugs can be designed to stop these mechanisms before they lead to major damage and legal blindness.

The first clinical sign of AMD is the formation of drusen, which appear as yellow spots in the fundus of the eye and whose mechanism of formation is unclear. Drugs that prevent drusen progression could cure AMD However, to develop these drugs, we need to understand how drusen form, and how aging and genes participate in this process. The most important genes associated with AMD belong to the complement system, which is an important part of the immune system that attacks bacteria. Mutations in these genes along with age, may cause the complement system to attack your own retinal cells inappropriately, which results in drusen formation. In our lab, we use retinal cells carrying typical mutations in complement genes to mimic the formation of drusen in a dish. This model helps to advance our understanding of why people with complement defects develop AMD, which is key for the design of drugs that can be administered as soon as drusen is detected, preventing disease progression to blindness.