A Comparison of the Retinal Microglial Cell Response to Injury

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DESCRIPTION (provided by applicant): I am committed to a career as a clinician scientist and this K08 award will help me realize this goal. My immediate career goal is to establish my own research laboratory. My long term career goal is to develop into a leader in the fields of regenerative medicine and cell based therapies. I graduated with an M.D., Ph.D. from Washington University School of Medicine and completed a postdoctoral research fellowship with Debora Farber, Ph.D. at UCLA. Currently, I hold an associate staff position at the Cole Eye Institute, Cleveland Clinic Foundation. In order to establish my laboratory, I currently see patients 25% of the time and conduct bench research 75% of the time. This award will allow me to maintain this ratio as I develop into an independent investigator and secure funding from an R01. My mentor and co-mentor for this proposal are Bela Anand-Apte, M.B.B.S, Ph.D. and Brian Perkins, Ph.D. Bela is a leader in the field of ocular angiogenesis and Brian is a leader in the field of retinal degenerations and is a zebrafish biologist. I enjoy a collaborative environmen with access to shared resources, personnel, and equipment as well as core facilities. They will closely supervise my progress and hold monthly meetings with me to discuss my career development and project progress. I will also meet quarterly with a career development advisory board consisting of my mentor, co-mentor, Dr. Joe Hollyfield, Dr. Neal Peachey, and Dr. John Crabb. I will also take intensive enrichment courses over the summer at Woods Hole and Cold Spring Harbor and courses at Case Western Reserve University School of Medicine. I am interested in looking at the role of scar formation and its effects on retinal regeneration. My hypothesis is the scar is inhibitory to regeneration in the retina. To test this hypothesis, I will investigate scar formation in mice and zebrafish. Mice and other mammals form scars in response to retinal injury. In contrast, zebrafish respond to retinal injury with a robust regenerative response. Microglial cells are surveyors of the retinal environment and they are believed to initiate the scar forming response in mammals. In this proposal we will compare the microglial cell response to a laser induced model of retinal injury in mice and zebrafish. Our specific aims are to (1) define the resident microglia response to injury in both organisms, (2) identify secreted factors which stimulate scar formation in an in vitro model, and (3) determine if inducing scar formation in zebrafish will inhibit retinal regeneration. This grant will allow us to better understand the different injury responses between these two species and will yield important information for future regenerative therapies in humans.