New Strategies for Modulation of Corneal and Ocular Surface Inflammation

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DESCRIPTION (provided by applicant): This is an application by Reza Dana, an associate professor at the Harvard Department of Ophthalmology, for a K24 Mid-Career Award to (i) provide him with protected time to devote more time to clinical and translational research activities, and to (ii) enhance his mentoring of new clinical investigators in the conduct of patient-oriented research. Dr. Dana is a clinician-scientist whose time is currently divided between (i) his laboratory where patient-oriented research is focused on determining the cellular mechanisms of corneal inflammation, (ii) his clinic focused on the management of patients with corneal and ocular inflammatory conditions, (iii) teaching of residents and fellows in ophthalmology, and (iv) various administrative duties in the Department of Ophthalmology. Due to this spread of responsibilities, protected time is limited for either expansion of clinical research activities or for focused mentoring of trainees and junior faculty colleagues. The current application, which has the strong backing of the institution and department chair, proposes 5 years of 25% effort support for Dr. Dana, which would greatly assist his further development as a clinician scientist and mentor by allowing him to limit 'pure' clinical care and hospital administrative functions as he expands clinical research and mentoring activities. The research plan is focused on development of novel therapeutic and/or prophylactic strategies for management of corneal and ocular surface inflammatory conditions. Specifically, the following clinical studies are envisioned: 1. Use of topical cyclosporine-A (CsA) for prevention of chronic ocular graft-versus-host disease (GVHD), wherein we hypothesize that initiation of topical cyclosporine A (CsA) treatment at the time of allergenic bone marrow or hematopoietic stem cell transplantation is efficacious for preventing the incidence and severity of ocular GVHD; and 2. Novel anti-cytokine strategies for management of ocular surface inflammation and corneal neovascularization (NV), wherein we propose to test molecular targeting strategies against specific cytokines known to be relevant in the pathogenesis of ocular surface inflammation. The overall health relevance of the proposed research is that advancing translational research in ophthalmology is of significant relevance to our public health, since there is a growing gap between the state of our basic science knowledge, which has grown considerably in the last decade, and the 'state of the art' in the clinical management of these conditions.