Approved Research

Refining genetic associations with age-related macular degeneration to facilitate their translation into viable therapeutic strategies

Lay summary

Age-related macular degeneration (AMD) affects close to 200 million individuals worldwide and accounts for approximately 15 to 20% of all causes of irreversible vision loss among individuals over 50 in Europe and North America. Patients with AMD experience years of visual impairments that may lead to acute and often permanent vision loss. Several genes have been implicated in the development of AMD. Understanding the role that variations within these genes play in the onset, progression and phenotypic presentation of AMD is key to designing effective therapies to prevent or treat this blinding disease.

Genetic associations with AMD have so far failed to be translated into effective therapeutic strategies and improved care for patients. This is partly due to the lack of refinement of genetic associations. Another reason is that methods traditionally applied to identify potential molecules and/or pathways to target to prevent or treat AMD often rely on genetic associations that have no direct link with observable molecular and functional changes that are known to drive the onset and progression of the disease.

The goal of this project is to identify variations within genes commonly associated with AMD that, when considered together, can describe the full spectrum of genetic susceptibility for this disease. Preliminary analyses indicate that this spectrum ranges from protection against the development of AMD to increased risk for disease onset. In addition, we aim to show that this spectrum of susceptibility can be entirely described by genetic variations that involve observable and quantifiable molecular and functional changes. Finally, we will demonstrate that our approach considerably improves our ability to assess the viability of candidate therapies against AMD when it is genetically driven.

The estimated duration of this project is 24 to 36 months. This work will considerably improve our chances of uncovering genotype-phenotype associations that can contribute to our understanding of the early molecular stages of AMD. In addition, it will considerably increase our ability to design precision guided therapies targeting forms of AMD that are genetically driven.