Can FDA-approved agents protect from PVR?

描述（由申请人提供）：增殖性玻璃体视网膜病变（PVR）是孔源性视网膜脱离视网膜再植手术失败的主要原因。虽然其发生率相对较低（约5-10%），但PVR仍然是一种难以治疗的疾病。除了20-40%的患者无法获得解剖成功的手术干预外，没有针对PVR患者的治疗方法，因此迫切需要为PVR患者开发非手术治疗方法。本提案的总体目标是证实和扩展我们最近的观察，即fda批准的某类眼病药物可以保护兔子免受PVR的影响，而不会对视网膜的整体形态或功能产生任何可检测到的影响。在这个项目中，我们将比较一组fda批准的药物保护兔子免受PVR的能力。将使用两种PVR模型；最常见和最具侵袭性（注射成纤维细胞），而更具有生理性（注射视网膜色素上皮细胞）。我们将用组织培养实验来补充这些动物研究，比较fda批准的一组药物来阻断玻璃体驱动的细胞反应（增殖、存活、迁移和收缩），这是PVR固有的。我们的研究结果将确定哪种药物能最好地预防实验性PVR，并开始确定靶向的细胞反应。我们预计，由于以下两个原因，拟议研究的结果将对预防PVR方法的发展产生持续而有力的影响。首先，目前没有策略可以降低患者发生PVR的风险。确定阻止动物发展PVR的药物将开始解决这一绊脚石，以保护患者免于屈服于PVR。其次，专注于fda批准的选择策略是将我们的发现转化为临床的最快方式。

DESCRIPTION (provided by applicant): Proliferative vitreoretinopathy (PVR) is the major cause for failure of retinal reattachment surgery for rhegmatogenous retinal detachment. While its occurrence is relatively low (approximately 5-10%) PVR remains a difficult disease to treat. With the exception of surgical intervention, for which 20-40% of the patients fail to achieve anatomical success, there is no treatment for individuals afflicted with PVR, and hence there is an acute need to develop non-surgical-based therapies for patients with PVR. The overall goal of this proposal is to confirm and extend our recent observation that a certain class of FDA-approved agents for ocular diseases protected rabbits from developing PVR without any detectable impact on the overall morphology or function of the retina. In this project we will compare the ability of a panel of FDA-approved agents to protect rabbits from developing PVR. Two PVR models will be used; the most common and aggressive (injection of fibroblasts), and the more physiological (injection of retinal pigment epithelial cells). We will complement these animal studies with tissue culture experiments that compare the panel of FDA-approved agents to block vitreous-driven cellular responses (proliferation, survival, migration and contraction) tht are intrinsic to PVR. Our findings will determine which agent prevents experimental PVR best, and begin to identify the cellular responses that are being targeted. We expect that the results of the proposed studies will have a sustained, powerful influence on the development of approaches to prevent PVR for the following two reasons. First, there are currently no strategies available to reduce a patient's risk of developing PVR. Identifying agents that prevent animals from developing PVR will begin to address this stumbling block to protecting patients from succumbing to PVR. Second, the strategy of focusing on options that are FDA-approved is the fastest way to translate our findings to the clinic.