The Increased Stiffness of Eye Tissues with Age may be Relevant to AMD
This proposal aims at bridging the gaps between normal aging and pathology of RPE/Bruch's membrane to identify therapeutic targets that can be used to stop AMD progression. In Aim 1, we will study the biochemical properties of macular vs. peripheral Bruch's membrane in eyes with AMD vs. controls. Further, we will evaluate if the elastic modulus of Bruch's membrane correlates with changes in composition. In aim 2, we will test if the biomechanics of the substrate play a role in RPE pathology. For that, we will measure cell functions and do transcriptomics in RPE cells grown on silk fibroin films. Im aim 3, we will use gene edited iPSC-derived RPE cells to study how the AMD risk alleles in CFH and HTRA1 contribute to the elastic modulus of the Bruch's membrane.
Previous studies have shown changes in the physical properties of the Bruch's membrane with age, but a precise characterization of the biomechanical properties of different areas of BrM in eyes with early AMD has not been performed to date. We anticipate that the elastic modulus of the Bruch's membrane has an impact on the RPE function, and this study may help to identify new pathways associated with RPE dysfunction that have not been addressed by existing studies or therapeutic approaches. Besides, The transmission of mechanical signals from the Bruch's membrane to the RPE can influence the survival of transplanted RPE cells in patients with advanced AMD. Thereby, the results of this project may help to improve the success of RPE transplantation in these patients.