Role of Photoreceptors in AMD

Project Summary

Our hypothesis is that AMD is caused by photoreceptors, more precisely, by age-related metabolic adaptations in photoreceptors. To test this hypothesis we have generated a new mouse model with altered cell metabolism in photoreceptors. This mouse model recapitulates many features of human AMD. The goal of this study is twofold: First, to determine to which extent our new mouse model mimics the human pathology, and second, to identify the metabolic change in photoreceptors that precipitates AMD in our mouse model. In Aim 1, we will focus on the metabolic changes in rod photoreceptors, and in Aim 2, we will focus on those occurring in cone photoreceptors to determine whether the metabolic changes in photoreceptors that cause AMD are the same between the night active rod photoreceptors and the day active cone photoreceptors. The uniqueness of this study is that it proposes a paradigm-shifting view of our understanding of how AMD develops. Putting photoreceptors at the center of AMD’s development allows us to answer many of the unresolved questions regarding this disease. Successful completion of the study will thus redirect research efforts in the field and lay the groundwork for many researchers to identify novel therapeutic targets that can delay disease onset.