Can FDA-approved agents protect from PVR?

FDA 批准的药物可以预防 PVR 吗？

• 批准号: 8589417
• 负责人: Andrius Kazlauskas
• 金额: $ 23.77万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8589417
• 关键词: Acute; Address; Animals; Avastin; Binding; Blood Platelets; Clinic; Complement; Data; Data Set; Development; Disease; Disease model; Dose; Exudative age-related macular degeneration; Eye; FDA approved; Failure; Family; Fibroblasts; Figs - dietary; Goals; Growth Factor; Immunoglobulin G; Individual; Injection of therapeutic agent; Light; Lucentis; Mann-Whitney U Test; Modeling; Morphology; Operative Surgical Procedures; Oryctolagus cuniculus; Pathogenesis; Patients; Physiological; Plasma; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor Receptor; Proliferative Vitreoretinopathy; Prophylactic treatment; Retina; Retinal; Retinal Detachment; Risk; Series; Staging; Structure of retinal pigment epithelium; Therapeutic; Translating; VEGF Trap; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; base; bevacizumab; diabetic; inhibitor/antagonist; intravitreal injection; macular edema; migration; novel; prevent; prophylactic; public health relevance; ranibizumab; research study; response; success; tissue culture

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.

描述（由申请人提供）：增生性玻璃体肾上腺病（PVR）是视网膜重新连接手术失败的主要原因。尽管它的发生相对较低（约5-10％），PVR仍然是一种难以治疗的疾病。除了手术干预外，20-40％的患者无法获得解剖学成功，没有针对患有PVR的个体的治疗方法，因此，对于PVR患者，急需开发基于非手术的疗法。 该提案的总体目的是确认并扩展了我们最近的观察结果，即一类FDA批准的眼部疾病保护兔子免于开发PVR，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批准的代理保护兔子免受PVR开发的能力。将使用两个PVR模型；最常见和侵略性的（注射成纤维细胞）和更生理的（注射视网膜色素上皮细胞）。我们将通过比较FDA批准的剂面板的组织培养实验来补充这些动物研究，以阻止玻璃体驱动的细胞反应（增殖，存活，迁移和收缩）与PVR具有固有的。我们的发现将确定哪种药物最能阻止实验性PVR，并开始确定目标的细胞反应。 我们预计，拟议研究的结果将对以下两个原因进行预防PVR的发展产生持续，强大的影响。首先，目前尚无降低患者患PVR风险的策略。识别防止动物发展PVR的药物将开始解决这个绊脚石，以保护患者免于屈服于PVR。其次，专注于FDA批准的选项的策略是将我们的发现转化为诊所的最快方法。