The Molecular Events in Early Life that lead to AMD
We aim to identify the molecular mechanisms by which lifestyle habits such as Western-style diets reprogram immune cells in the eye throughout life, making them susceptible to trigger age-related macular degeneration (AMD).
1) We will investigate if a past history of obesity triggers a persistent memory state in immune cells and predisposes to heightened inflammation and AMD. We developed a mouse model that allows us to render mice obese and subsequently make them lose weight to study behaviour of immune cells in the eye and in AMD. 2) We will assess if past obesity induces long term changes in genes of immune cells. We will also identify the immune cells that are affected and that exacerbate AMD. 3) We will explore if interfering with the genetic changes in immune cells brought upon by obesity can improve AMD.
While there have been significant efforts placed on identifying genetic predispositions to various forms of AMD, there are presently only treatments available for the wet form of disease. The current research project explores the root causes of AMD and seeks to identify a molecular mechanism that explains why genetics are relatively poor predictors of who will ultimately develop AMD. The studies will explore why environmental factors are important predictors of disease or may compound the effects of genetic predisposition.
AMD is a leading cause of blindness in industrialized countries. This study will aim to identify how early life metabolic stressors, such as those collectively linked to obesity, can drive a disease of aging such as AMD, and this long after metabolic equilibrium is reestablished. Ultimately, findings from this research may identify causes, potential therapeutics or prognostic tools for AMD.