Can FDA-approved agents protect from PVR?

FDA 批准的药物可以预防 PVR 吗？

• 批准号: 8423923
• 负责人: Andrius Kazlauskas
• 金额: $ 29.1万
• 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/8423923
• 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）：复发性玻璃体视网膜病变（PVR）是孔源性视网膜脱离视网膜复位手术失败的主要原因。尽管其发生率相对较低（约5-10%），但PVR仍然是一种难以治疗的疾病。除了手术干预（20-40%的患者未能实现解剖学成功）之外，没有针对患有PVR的个体的治疗，因此迫切需要开发用于患有PVR的患者的基于非手术的疗法。 本提案的总体目标是证实和扩展我们最近的观察结果，即FDA批准的某类眼科疾病药物可保护家兔免于发生PVR，而对视网膜的整体形态或功能无任何可检测的影响。在这个项目中，我们将比较一组FDA批准的药物保护家兔免于发生PVR的能力。将使用两种PVR模型;最常见和侵袭性的（注射成纤维细胞）和更生理性的（注射视网膜色素上皮细胞）。我们将通过组织培养实验补充这些动物研究，比较FDA批准的药物组阻断玻璃体驱动的细胞反应（增殖，存活，迁移和收缩），这些反应是PVR固有的。我们的研究结果将确定哪种药物最能预防实验性PVR，并开始识别目标细胞反应。 我们期望这些研究的结果将对预防PVR的方法的发展产生持续的、强有力的影响，原因有以下两个。首先，目前没有可用于降低患者发生PVR的风险的策略。确定防止动物发生PVR的药物将开始解决这一障碍，以保护患者免于死于PVR。其次，专注于FDA批准的选择的策略是将我们的发现转化为临床的最快方式。