Grant: Operating Grant

Age related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly. Each year 80,000 Canadians are diagnosed with a form of AMD. At present, there are an estimated 1 million people in Canada with AMD, and this number is expected to double by 2031. There are treatments to slow the progression of AMD and vision loss, but we do not know how to prevent AMD from occurring. In order to prevent AMD, we need to know more about how and why AMD develops. Earlier studies identified that AMD is a disease in which the photoreceptor cell in the retina degenerates and eventually dies. These cells do not regenerate. Once these cells die, they are never replaced. The loss of the photoreceptor cell causes blindness. Neighboring cells in the eye, the retinal pigment epithelial cells (RPE), support and maintain the health of the photoreceptor cell. However, in AMD, RPE do not function normally, and therefore they no longer support the photoreceptor cell. We will determine what causes the RPE cells to become abnormal in the early stages of AMD. Drusen accumulate near the RPE. Drusen are a hallmark of the early stage or 'dry' form of AMD. We will focus on two components of drusen, advanced glycation end products (AGEs) and amyloid beta. Our experiments will focus on the effects of these two abnormal products on RPE function. We showed that these products caused RPE to abnormally secrete cytokines. These cytokines promote swelling and inflammation in the retina. Our hypothesis is that AGEs and amyloid beta cause RPE to change their gene expression patterns, with these newly induced gene products causing retinal inflammation. Inflammation is known to promote AMD. If proven correct, we will be the first to show that drusen components, specifically AGEs and amyloid beta, cause pro-inflammatory events in the eye. These results will allow us to develop novel first-in-class strategies using AGEs and amyloid beta as targets to prevent and treat AMD.