Progressive photoreceptor loss due to disease or trauma leads to irreversible blindness throughout the USA. Transplantation of photoreceptors derived from stem cells offers exciting potential for restoring vision, but the overarching challenge is to achieve functional integration within the complex retinal architecture. Surprisingly, the role of the retinal motogenic environment in the positioning and integration of transplanted photoreceptor precursor cells (PPCs) remains largely unexplored. Our group has reported that PPC subsets exhibit distinct migratory responses to dose-dependent signaling from EGF and SDF-1: These molecules are well-known to activate receptor-mediated chemotaxis and are abundant in adult retinal laminae. It is our hypothesis that PPC integration will be improved by selectivity for subpopulations able to chemotactically navigate the complex microenvironments of damaged retina. This project will cultivate a unique combination of microfluidics and explant retina models to enable selectivity for PPCs with honing migratory capabilities (HM-PPCs) to a range of concentration gradients present in light-damaged retina (as a model). Experiments will then evaluate the extent to which HM- PPCs populations integrate within retinal laminae.
Photoreceptor failure in the retina is a major cause of adult vision loss in the USA. Transplantation of stem cells into damaged retina offers exciting potential for restoring vision, but restored visual response is limited by the poor integration of transplanted cells into retinal laminae. Our project directly addresses the nature of chemotactic signaling produced by adult retinal tissue and how these signals can be used to establish photoreceptor progenitor cell (PPC) synaptic integration into damaged retina. Successful outcomes will enable selectivity for PPC subpopulations with honing migratory capabilities specific to retinal microenvironments, as well as assess functionality of cell integration within retinal laminae.