Pharmacological Treatment of Retinal Diseases

来自药理学系的跨学科研究者联盟， 凯斯西储大学的眼科学和生物医学工程， 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， 翻译成复杂的视觉系统障碍和疾病的治疗方法”，这是R24国家计划的既定目标。 眼科研究所（NEI）视觉障碍治疗转化研究计划。这一科学 合作伙伴将利用其多样化的科学专长来表征和测试视网膜病变的潜在疗法。 疾病的动物模型，通过使用尖端的生理，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， 在模拟Stargardt病、年龄相关性黄斑变性的动物模型中预防视网膜病变 (AMD)和视网膜色素变性（RP），我们将在人体试验前加速药物开发。 作为这些实验的一个组成部分，改善药物向眼睛的输送也将是一个高度优先事项。 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 （2）评估全反式视网膜在眼睛中的类似物，并防止其凝结为有害的共轭物; FDA批准的药物作为潜在的先导化合物，通过使用批准的 在动物模型研究中发现有效和安全的化合物;（3）评估生物利用度和分布 这些试剂以确定它们渗透和保留在眼睛中而不影响正常的能力。 光传导和视觉循环反应;（4）探索不同的药物输送模式， 提供在眼睛中的治疗药物浓度的新型生物可降解聚合物。最终 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， 患有目前无法治愈的致盲疾病的患者。 相关性（参见说明）： 美国法定盲人人数超过130万，其中约有800万至1000万人老龄化。 将受年龄相关性黄斑变性（AMD）影响的人。机械地利用 Stargardts病的相关模型，我们已经证明了快速筛查可能重新利用 一系列FDA批准的分子这一提议提供了一个令人信服的机会， riisfiasfi and 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.