Photoreceptor integration via chemotactic honing

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 DESCRIPTION (provided by applicant): 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.