New Strategies for Modulation of Corneal and Ocular Surface Inflammation

描述（由申请人提供）：这是哈佛眼科系副教授Reza Dana申请K24职业中期奖的申请，以（i）为他提供受保护的时间，将更多时间投入临床和转化研究活动，以及（ii）加强他对新临床研究者进行以患者为导向的研究的指导。Dana博士是一名临床科学家，目前他的时间分为（i）他的实验室，以患者为导向的研究重点是确定角膜炎症的细胞机制，（ii）他的诊所专注于角膜和眼部炎症患者的管理，（iii）眼科住院医师和研究员的教学，以及（iv）眼科部门的各种行政职责。由于这种责任的传播，受保护的时间是有限的，无论是临床研究活动的扩展或学员和初级教师同事的重点指导。目前的申请得到了机构和系主任的大力支持，为Dana博士提供了5年25%的努力支持，这将极大地帮助他作为临床科学家和导师的进一步发展，使他能够在扩大临床研究和指导活动时限制“纯粹”的临床护理和医院管理职能。该研究计划的重点是开发新的治疗和/或预防策略，用于管理角膜和眼表炎症性疾病。具体而言，设想以下临床研究：1.局部环孢菌素A（CsA）用于预防慢性眼部移植物抗宿主病（GVHD）的用途，其中我们假设在过敏性骨髓或造血干细胞移植时开始局部环孢菌素A（CsA）治疗对于预防眼部GVHD的发生率和严重性是有效的;和2.用于管理眼表炎症和角膜新生血管（NV）的新型抗细胞因子策略，其中我们提出测试针对已知与眼表炎症发病机制相关的特定细胞因子的分子靶向策略。拟议研究的整体健康相关性是，推进眼科转化研究与我们的公共卫生具有重要意义，因为我们的基础科学知识在过去十年中大幅增长，与这些条件的临床管理中的“最先进水平”之间存在越来越大的差距。

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.