The Role of Primary Cilia in RPE and Macular Degeneration
MentorYang Sun, MD, PhD
The goal of this project is to advance our understanding of how primary cilia participate in RPE repair in vivo and provide a potential target for AMD patients. In our preliminary data, we have demonstrated that defective cilia promote RPE wound healing by controlling proliferation. In aim 1, we investigate whether INPP5E, a key component of primary cilia, plays a role in RPE repair and proliferation. In aim 2, we investigate whether the effect of phosphoinositide balance, which regulates proliferation, is involved in the RPE repair process.
We (1) utilized a laser-induced RPE injury model that limits RPE damage to traceable regions within the rodent RPE. (2) utilized a novel transgenic mouse that can consistently induce Cre activity in 80-90% of RPE cells, whereas expression is less effective in the BEST1-Cre mouse line. (3) utilizes floxed mice to maximize the physiological relevance of the results through virus-based gene expression and high-resolution microscopy. This proposal aims to investigate RPE cilia's role in vivo and related signaling pathways. To our knowledge, there is no study that links cilia and AKT signaling in mouse RPE, and it would have a significant impact on cilia biology. If our hypotheses are correct, the proposed experiments will likely identify a novel mechanism for AMD repair and, consequently, open new therapeutic strategies.