Studies of Retinopathy of AIDS in the HAART Era

HAART时代艾滋病视网膜病变研究

• 批准号: 7062487
• 负责人: William R. Freeman
• 金额: $ 60.2万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-12-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7062487
• 关键词: AIDS; antiviral agents; clinical research; cytomegalovirus retinitis; cytosine analog; disease /disorder proneness /risk; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; electroretinography; eye disorder chemotherapy; eye pharmacology; guinea pigs; human subject; human therapy evaluation; laboratory rabbit; longitudinal human study; medical complication; opportunistic infections; pharmacokinetics; polymerase chain reaction; retina circulation disorder; uveitis

DESCRIPTION (provided by applicant): Individuals infected with HIV are well known to develop both infectious retinopathies (e.g., Cytomegalovirus Retinitis) and non-infectious retinopathies (e.g., retinal microvascular occlusions such as cotton wool spots). In the era of HAART, these problems still occur and manifest in tests of vision function, as well as by ophthalmologic examinations, and in the case of infectious CMV retinitis, may still result in severe vision loss and blindness due to resistant CMV retinitis in patients who are not responding well to, or who cannot reliably take, HAART therapy. Infectious retinitis and low CD4 counts, which predispose to non-infectious retinopathy, are more common in minority groups. This grant uses new technologies and novel methods to achieve three related goals. The first goal is to determine the prevalence and severity of the visual dysfunction that we have observed in HAART era HIV patients that are free of infectious retinitis. This work will be done through a longitudinal observational study that will employ a variety of non and minimally invasive vision testing methods, including new types of visual field tests and the multifocal ERG, which can accurately measure the location of retina! signals generated during the vision process. Second, we have shown that retinal cotton wool spots, which cause permanent retinal and visual defects, form even in patients on HAART. We hypothesize that the cumulative effect of these lesions, together with other areas of retinal vessel damage, leads to widespread retinal changes that account for the visual field loss we have shown. We will study retinal cotton wool spots obtained from autopsy eyes through our collaboration with the California NeuroAIDS Tissue Network (CNTN). Such studies will employ new, highly sensitive and specific molecular methods such as TAQMan PCR to determine the molecular basis of these lesions. Third, we wish to further our work on local anti-CMV treatments and to pursue our new discovery: Namely, the ability to crystallize nucleoside and nucleotide analogues with potent high anti-CMV activity. Injection of such crystals into eyes with CMV retinitis will result in slow dissolution of these crystals and an extremely long acting injectable anti-CMV drug preparation.

描述（由申请人提供）：众所周知，感染 HIV 的个体会出现传染性视网膜病（例如，巨细胞病毒性视网膜炎）和非传染性视网膜病（例如，视网膜微血管闭塞，如棉絮斑）。在HAART时代，这些问题仍然会出现并表现在视力功能检查以及眼科检查中，而在感染性CMV视网膜炎的情况下，仍然可能导致患者因抵抗性CMV视网膜炎而导致严重的视力丧失和失明。对 HAART 治疗反应不佳或不能可靠地接受 HAART 治疗的人。感染性视网膜炎和低 CD4 计数容易导致非感染性视网膜病，在少数群体中更为常见。 该赠款使用新技术和新方法来实现三个相关目标。第一个目标是确定我们在HAART时代无传染性视网膜炎的HIV患者中观察到的视觉功能障碍的患病率和严重程度。这项工作将通过纵向观察研究来完成，将采用多种无创和微创视力测试方法，包括新型视野测试和多焦ERG，可以准确测量视网膜的位置！视觉过程中产生的信号。其次，我们已经证明，即使在接受 HAART 的患者中，也会形成视网膜棉絮斑，从而导致永久性视网膜和视力缺陷。我们假设这些病变的累积效应与视网膜血管损伤的其他区域一起导致广泛的视网膜变化，从而导致我们所显示的视野丧失。我们将通过与加州神经艾滋病组织网络 (CNTN) 的合作，研究从尸检眼睛中获得的视网膜棉絮斑。此类研究将采用新的、高度敏感和特异性的分子方法，例如 TAQMan PCR 来确定这些病变的分子基础。第三，我们希望进一步开展局部抗 CMV 治疗的工作，并追求我们的新发现：即能够结晶具有强效高抗 CMV 活性的核苷和核苷酸类似物。将此类晶体注射到患有 CMV 视网膜炎的眼睛中将导致这些晶体缓慢溶解，并形成极长效的可注射抗 CMV 药物制剂。