Biomechanical properties of the Bruch’s membrane and their relevance to the RPE pathology in 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.

Age-related macular degeneration (AMD) is the major cause of visual impairment in developed countries, affecting 196 million people worldwide. Unfortunately, there is no cure for AMD. The complex origin and the limited understanding of the disease mechanisms make it challenging to develop efficient treatments.
While the specific mechanisms that lead from normal aging to AMD pathology are unknown, we have observed similar features between eyes with AMD and fibrotic processes in other organs. Therefore, we think that the diminished elasticity of the retina with age may play a critical role in AMD progression. We also believe that the stiffness of the eye may impede the integration and survival of retinal cells used in replacement therapy in patients with advanced AMD, especially in the presence of genetic risk variants.
It is possible that the stiffness of alters the functional support of the ocular tissue, leading to the impairment of the retinal cells sitting on top, which eventually stop functioning and result in vision loss. In this proposal, we will evaluate the rigidity of eyes with and without AMD and how the elasticity of the substrate impacts the function of the retinal cells. The results will contribute to bridge the gaps between aging and AMD as well as to improve existing therapeutic approaches for AMD patients, such as the RPE transplantation.

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.