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: 7599582
• 负责人: William R. Freeman
• 金额: $ 59.45万
• 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/7599582
• 关键词: AIDS neuropathy; Accounting; Acquired Immunodeficiency Syndrome; Antiviral Agents; Area; Autopsy; Biological Assay; Blindness; CD4 Lymphocyte Count; California; Collaborations; Cytomegalovirus; Cytomegalovirus Retinitis; Defect; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Eye; Functional disorder; Funding; Goals; Grant; HIV; HIV Infections; Highly Active Antiretroviral Therapy; Individual; Infarction; Inflammatory; Injectable; Injection of therapeutic agent; Lead; Lesion; Lipids; Location; Measures; Messenger RNA; Methods; Minority Groups; Molecular; National Institute of Mental Health; Nucleosides; Nucleotides; Observational Study; Pathogenesis; Patients; Pharmaceutical Preparations; Prevalence; Process; Psychophysiology; Quality of life; Research; Research Personnel; Resistance; Retina; Retinal; Retinal Diseases; Retinitis; Risk Factors; Severities; Side; Signal Transduction; Surface; Techniques; Testing; Tissues; Viral; Viral Genome; Viral Load result; Vision; Vision Tests; Visual; Visual Fields; Water; Work; base; cohort; cotton wool spots; cytokine; inflammatory marker; innovation; minimally invasive; neurobehavioral; new technology; non-compliance; novel; nucleotide analog; particle; programs; retina blood vessel structure

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）：感染HIV的个体众所周知，既发展感染性视网膜病（例如巨细胞病毒视网膜炎）和非感染性视网膜病（例如，视网膜微血管遮挡，例如棉质羊毛斑点）。在Haart时代，这些问题仍在发生，并且在视力功能的测试以及眼科检查中以及在感染性CMV视网膜炎的情况下，仍可能导致因无法响应或无法响应的患者的抵抗力CMV视网膜炎而导致严重的视力丧失和失明，HAART治疗，Haart治疗。在少数群体中，传染性视网膜炎和低CD4计数易感性视网膜病变易受感染性视网膜病。 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 ERA HIV患者中观察到的视觉功能障碍的患病率和严重程度。这项工作将通过一项纵向观察研究来完成，该研究将采用多种非侵入性视力测试方法，包括新型的视野测试和多灶性ERG，可以准确测量视网膜的位置！在视觉过程中产生的信号。其次，我们已经表明，即使在HAART的患者中，也会形成永久性视网膜和视觉缺陷的视网膜棉布斑点。我们假设这些病变的累积作用以及视网膜血管损伤的其他区域会导致广泛的视网膜变化，这些变化占了我们所显示的视野损失。我们将通过与加利福尼亚神经辅助组织网络（CNTN）的合作来研究从尸检眼中获得的视网膜棉布斑点。此类研究将采用新的，高度敏感和特定的分子方法（例如Taqman PCR）来确定这些病变的分子基础。第三，我们希望进一步在局部抗CMV处理方面的工作，并追求我们的新发现：即，具有有效的高抗CMV活性的核苷和核苷酸类似物的能力。将这种晶体注射到CMV视网膜炎中，将导致这些晶体缓慢溶解，并且表现出极长的可表现的注射抗CMV药物制剂。