The overall goal of this proposal is to provide the Candidate with the education, skills, and experiences to become an independent researcher studying corneal wound healing and ocular optics. The clinical-research focus is on endothelial keratoplasty (EK), a corneal transplant procedure in which the patient's diseased endothelium and Descemet's membrane are removed and replaced with the posterior third of a donor cornea with healthy endothelium. The scientific focus of this proposal is to gain a better understanding of the cell biology and tissue interactions involved in the wound healing response following EK and their subsequent effects on ocular optics. Keratocyte activation and myofibroblast differentiation create haze and cause decreased vision and refractive regression following photorefractive keratectomy and incisional wounds. Endothelial failure accounts for almost one half of the corneal transplants that are performed. EK procedures have now gained widespread acceptance because of the faster recovery, less astigmatism, and greater wound stability. Despite these advantages over traditional corneal transplants, vision remains limited post-operatively. Better visual outcomes may come through improved understanding of wound healing at the stromal graft interface.The hypothesis to be tested is that the interface haze following EK is mediated by keratocyte activation and myofibroblast differentiation, reducing vision by increasing light scatter and higherorder optical aberrations. Better characterization of these changes and cellular pathways involved may suggest rational therapies for their modulation and allow for improved visual outcomes. To address this hypothesis, two specific aims are proposed: Aim 1 assesses in vivo corneal wound repair at the EK interface and its growth factor control over time. These changes will be correlated with changes in ocular optics and with ex vivo histopathology in humans and in a cat model. Aim 2 modulates the wound healing response with pharmacological agents with the goal of improving transparency and optics. In addition to the proposed research focusing on cell biology and tissue interactions, the PI will receive invaluable didatic training in optics at the Optics Institute, in vision optimization research at the University of Rochester Center for Visual Science, and will form meaningful collaborations with other investigators in the Clinical and Translational Science Institute while completing a Master of Science in Translational Research.