New Strategies for Modulation of Corneal and Ocular Surface Inflammation

描述(由申请人提供)：这是哈佛大学眼科副教授Reza Dana申请K24职业中期奖的申请，目的是(I)为他提供更多的时间用于临床和转化性研究活动，以及(Ii)在以患者为导向的研究中加强对新临床研究人员的指导。达纳博士是一名临床科学家，他目前的工作包括：(I)他的实验室，以患者为中心的研究集中于确定角膜炎症的细胞机制；(Ii)他的诊所专注于管理患有角膜和眼部炎症的患者，(Iii)教授住院医生和研究员眼科，以及(Iv)眼科的各种行政职责。由于责任的分散，受保护的时间无论是用于扩大临床研究活动，还是用于对受训者和初级教员同事进行重点指导都是有限的。目前的申请得到了该机构和科室主任的大力支持，建议为Dana博士提供5年25%的努力支持，这将极大地帮助他进一步发展成为一名临床科学家和导师，允许他在扩大临床研究和指导活动的同时限制“纯”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状况。具体地说，临床研究设想如下：1.使用局部环孢素A(CsA)预防慢性眼部移植物抗宿主病(GVHD)，其中我们假设在致敏性骨髓或造血干细胞移植时开始局部环孢素A(CsA)治疗对于预防眼部GVHD的发生和严重程度是有效的；以及2.治疗眼表炎症和角膜新生血管(NV)的新的抗细胞因子策略，其中我们提出了针对已知在眼表炎症发病机制中相关的特定细胞因子的分子靶向策略。这项拟议研究的整体健康相关性是，推进眼科转化研究对我们的公共健康具有重要意义，因为在过去十年中，我们的基础科学知识与这些疾病的临床管理的“最新水平”之间存在着越来越大的差距。

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.