Epigenetic Dissection of Age-Related Macular Degeneration

Given the development of anti-angiogenic agents, vision loss resulting from neovascular, ‘wet,’ and age-related macular degeneration (AMD) should be largely preventable if diagnosed early. Methylation patterns of AMD-related genes should identify subjects who are at high risk of neovascular AMD. Ultimately, this project could lead to the development of diagnostic tests and identify novel treatment pathways that modify gene expressions.

Given the development of anti-angiogenic agents, blindness resulting from neovascular AMD should be largely preventable if diagnosed early. Identifying individuals predisposed to severe forms of this debilitating disease will, in time, help optimize the use of finite treatment resources. Methylation patterns, or characteristic patterns of chemical modifications to the DNA of AMD-related genes, should identify subjects who are at high risk of neovascular AMD. Ultimately, this project will lead to the development of diagnostic tests and identify novel treatment pathways that modify gene expression.

Our research approach to investigate gene expression of AMD in a large scale genome-wide methylation study with subgroup analyses by disease severity is novel. The investigators on this study represent a strong collaboration comprising clinician-scientists, statisticians and epigeneticists whose collective expertise will ensure its successful completion.

Progress Updates

Epigenetics is the study of inheritance that isn’t related to the spelling of a person’s genes, but caused by various exposures (such as smoking, dietary intakes, …) that can influence the DNA backbone that may affect how a gene gets expressed. In this study, Dr. Wang’s and Dr. Hewitt’s team are looking for an epigenetic modification called “methylation.” So far, they have identified a number of epigenetic variants associated with exudative (wet) age-related macular degeneration. The team has compared the entire “epigenome” of patients with macular degeneration to the epigenomes of people without macular degeneration, and has found several methylation sites that are associated with the disease. These parts of the genome were not previously known to be involved with an increased risk of macular degeneration. The team is currently validating their initial findings, and determining how these epigenetically-modified genes act to increase the risk of getting macular degeneration.