The Role of Ubiquilin 2 in Age-Related Macular Degeneration

This proposal aims to investigate the early changes in age-related macular degeneration (AMD), focusing on the components of drusen, abnormal aggregations of protein and lipids which build up in the retina in AMD. We will focus our studies on one component of the sub-cellular system that is responsible for breaking down damaged proteins within each cell in the body. Our target protein, ubiquilin 2, plays an important role in this system, but its function in the eye has never before been studied. Our preliminary data show that ubiquilin 2 collects in drusen and that, in mice, ubiquilin 2 may be necessary for the eye’s ability to break down damaged proteins. We will use donated tissue samples from AMD patients and people without AMD to investigate ubiquilin 2’s function in the human eye. Specifically, we will determine where in the eye ubiquilin 2 is found and which components of the protein recycling system it interacts with. These experiments will provide the foundation for future investigations of ubiquilin 2’s function in human retinal cells and in mice. Together, these studies will address an important gap in our understanding of how the eye’s ability to break down damaged proteins fails in AMD, and they will open promising new avenues for research which could ultimately lead to the development of new treatments to delay or prevent the progression of AMD.