Grant: Project Grant

As our population ages, age-related eye diseases are becoming more common. Prominent among these is age-related macular degeneration, affecting 2.5 million Canadians and nearly 200 million people worldwide. This disease comes in two forms, causing blindness either slowly by death of the light-sensing cells in the retina (dry AMD), or quickly by the formation of abnormal new blood vessels under the retina (wet AMD). Although therapies exist for wet AMD and the advanced form of dry AMD, these must be injected into the eye, and no therapies are available for early stages of AMD. Therefore, there is a pressing need to find new targets. To this end, we have identified an enzyme in eye cells called soluble epoxide hydrolase (sEH). sEH modifies fat molecules to change their biological properties and can promote inflammation and blood vessel growth. We have previously shown that drugs that block sEH can decrease the kind of blood vessel growth that occurs in wet AMD and can decrease inflammation in eye cells. Therefore, we think sEH could be an exciting new drug target for treating both dry and wet AMD. We propose to explore this by assessing how sEH functions in the eye cells that are damaged first in AMD, in an effort to understand the early stages of AMD. We will determine which fat molecules are modulated by sEH in these cells and how sEH inhibition changes the cells' properties and those of neighbouring blood vessel and immune cells. Then, we will test sEH inhibition in animal models with features of dry and wet AMD. We expect that sEH will prove to be important for AMD disease onset and progression and validate it as a promising therapeutic target. sEH inhibitors already developed are safe and can be taken as pills, raising the possibility of a new kind of therapy for both dry and wet AMD.