New Strategies for Modulation of Corneal and Ocular Surface Inflammation

描述（由申请人提供）：这是哈佛大学眼科系副教授Reza Dana申请K24中期职业奖的申请，旨在(i)为他提供受保护的时间，以便将更多的时间投入到临床和转化研究活动中，以及（ii）加强他对新的临床研究人员进行以患者为导向的研究的指导。Dana博士是一名临床医生兼科学家，他的时间目前被划分为(i)他的实验室，以患者为导向的研究侧重于确定角膜炎症的细胞机制，（ii）他的诊所侧重于角膜和眼部炎症患者的管理，（iii）眼科住院医生和研究员的教学，以及（iv）眼科的各种行政职责。由于责任的分散，无论是扩大临床研究活动，还是集中指导学员和初级教员同事，保护时间都是有限的。目前的申请得到了机构和系主任的大力支持，建议为Dana博士提供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，允许他在扩大临床研究和指导活动的同时，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，以管理角膜和眼表炎症。具体而言，设想以下临床研究：1。使用局部环孢素A （CsA）预防慢性眼部移植物抗宿主病（GVHD），其中我们假设在致过敏性骨髓或造血干细胞移植时开始局部环孢素A （CsA）治疗可有效预防眼部移植物抗宿主病的发生率和严重程度；和2。治疗眼表炎症和角膜新生血管（NV）的新型抗细胞因子策略，其中我们建议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，推进眼科的转化研究与我们的公共卫生具有重要相关性，因为我们的基础科学知识水平在过去十年中大幅增长，与这些疾病的临床管理中的“最新技术”之间的差距越来越大。

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.