Genetics of age-related macular degeneration: Application to drug design

摘要

Although age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, treatment options are currently limited by a lack in the full understanding of disease pathogenesis. Much work has shown AMD pathogenesis to involve the complex interaction of genetic and environmental factors. While environmental factors such as smoking can directly result in a significant increase of risk, family and twin studies have long shown AMD to contain a significant genetic component and genome-wide studies have revealed an association between AMD susceptibility and polymorphisms in immune-related genes, most notably in CFH and ARMS2/HTRA1. Technological advances have made genetic associations increasingly easy to identify; however, several key issues subsist in translating newly available genetic information into effective clinical therapy. Unlike monogenic retinal diseases, AMD is a complex disorder that involves the interaction of multiple genetic loci and does not have a direct therapeutic target. In AMD, gene-gene interactions and their risk conferment are still unclear. Interaction between specific polymorphisms in CFH and ARMS2IHTRA1 has been well demonstrated, but several studies report contradicting results. The lack of consistent conclusions in gene-gene interaction studies hints at complexity that needs further study before advancing to clinical application.