Pharmacological Treatment of Retinal Diseases

一个由药理学部门的研究人员组成的跨学科联盟， 凯斯西储大学眼科和生物医学工程 辛辛那提大学药物发现中心、华盛顿大学和宾夕法尼亚大学， 建议“加快疾病机制的基础科学发现的步伐” 转化为复杂视觉系统障碍和疾病的治疗“，这是R24国家 眼科研究所(NEI)视力障碍治疗的翻译研究计划。这是科学的 合作伙伴公司将利用其不同的科学专业知识来表征和测试潜在的视网膜疗法 动物模型中的疾病，使用尖端的生理、化学、分析和 成像方法。通过筛选食品和药物管理局(FDA)批准的药物的能力 在模拟Stargardt病、老年性黄斑变性的动物模型中预防视网膜病理 对于黄斑变性(AMD)和视网膜色素变性(RP)，我们将在人体试验之前加快药物开发。 作为这些实验的一个组成部分，改善药物对眼睛的传递也将是一个高度优先的问题。 该项目的具体目标是：(1)测试FDA批准的药物降低毒性水平的能力 眼部全反式视黄醇，防止其凝结成有害的结合物；(2)评估类似物 FDA批准的药物作为治疗视网膜疾病的潜在先导化合物 在动物模型研究中发现化合物有效和安全；(3)评估药物的生物利用度和分布 这些药物能够在不影响正常的情况下穿透并留在眼睛里 光传导和视觉循环反应；以及(4)探索不同的药物输送方式和发展 新型可生物降解聚合物，可在眼睛中提供治疗药物浓度。归根结底， 这些相互关联的目标的实验结果将指导我们开发更成功的治疗方法 受目前无法治愈的致盲疾病影响的患者。 相关性(请参阅说明)： 美国法定失明人数超过130万，老年人口约为800万至1000万 将受到年龄相关性黄斑变性(AMD)影响的人群。机械地使用一个 在Stargardts病的相关模型中，我们已经演示了快速筛查可能重新定位 广泛的FDA批准的分子。这一提议提供了一个令人信服的机会来攻击这一不幸的 Riisfiasfi和nthsr cnnditinn.c；inditriinn AMD。

An interdisciplinary consortium of investigators from the Departments of Pharmacology, Ophthalmology and Biomedical Engineering at Case Western Reserve University in collaboration with the University of Cincinnati Drug Discovery Center, Washington University and the University of Pennsylvania, proposes "to increase the pace at which basic science discoveries on disease mechanisms can be translated into therapies for complex visual system disorders and disease", a stated goal of the R24 National Eye Institute (NEI) Translational Research Program on Therapy for Visual Disorders. This scientific partnership will employ its diverse scientific expertise to characterize and test potential therapies for retinal diseases in animal models by using a combination of cutting-edge physiological, chemical, analytical and imaging approaches. By screening Food and Drug Administration (FDA)-approved drugs for their ability to prevent retinal pathology in animal models that mimic Stargardt's disease, age-related macular degeneration (AMD), and retinitis pigmentosa (RP), we will accelerate drug development before testing in humans. Improving drug delivery to the eye as an integral part of these experiments will also be a high priority. Specific goals of this project are to: (1) Test FDA-approved drugs for their ability to reduce toxic levels of all-trans-retinal in the eye and prevent its condensation to harmful conjugates; (2) Evaluate analogues of FDA-approved drugs as potential lead compounds for treating retinal diseases by using approved compounds found effective and safe in animal model studies; (3) Assess the bioavailability and distribution of these agents to determine their ability to penetrate and remain in the eyes without affecting normal phototransduction and visual cycle reactions; and (4) Explore different modes of drug delivery and develop novel biodegradable polymers that provide therapeutic drug concentrations in the eyes. Ultimately, the experimental results of these interrelated aims will guide us in developing more successful therapies for patients affected by currently incurable blinding diseases. RELEVANCE (See instructions): The number of persons who are legally blind in the USA exceeds 1.3 million with about 8-10 million aging persons who will be affected with age-related macular degeneration (AMD). Utilizing a mechanistically relevant model of Stargardts disease, we have demonstrated rapid screening to potentially repurpose a broad set of FDA approved molecules. This proposal offers a compelling opportunity to attack this grievous riisfiasfi and nthsr cnnditinn.c; inditriinn AMD.