Applying Low Levels of Strain to Model Nascent Phenomenon of Retinal Pathologies

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. A better understanding of the mechanisms of the disease, especially at early stages, could elucidate new treatment targets. One characteristic of AMD is strain on the retinal pigment epithelium (RPE), a crucial layer of the retina. This strain can be caused by physical phenomena like waste aggregation underneath the RPE from aging, drusen formation, or leaky blood vessels that infiltrate the retina during choroidal neovascularization (CNV). It is not well understood how strain affects RPE cells. Most models generate equibiaxial strain or higher levels of strain that are not representative of early stages of AMD. To overcome these issues, we have engineered a device to cause controlled, low amounts of localized, radial strain (maximum ~2%). This strain level is more mimetic to what occurs during aging or at the beginning of physical disruptions experienced during AMD. To evaluate how RPE cells respond to this physical stimulus, primary porcine RPE cells were exposed to low levels of strain applied by our custom-made device. Cell secretions and genetic expression were analyzed to see how proteins linked to drusen and CNV are affected. The results indicate that this low amount of strain does not immediately initiate angiogenesis but causes changes in mRNA expression of amyloid precursor protein (APP), which plays a role in retinal health and drusen accumulation. This research offers insight into AMD progression as well as the health of other organs, including the brain.