Studies of Retinopathy of AIDS in the HAART Era

描述(由申请人提供)：众所周知，感染艾滋病毒的人既会发展为感染性视网膜病变(如巨细胞病毒视网膜炎)，也会发展为非传染性视网膜病变(例如视网膜微血管闭塞，如棉毛斑)。在HAART时代，这些问题仍然会出现，并在视觉功能测试和眼科检查中表现出来，在感染性CMV视网膜炎的情况下，对于对HAART治疗没有良好反应或不能可靠地接受HAART治疗的患者，由于抗药性CMV视网膜炎，仍然可能导致严重的视力丧失和失明。感染性视网膜炎和低CD4计数易患非感染性视网膜病变，在少数族裔人群中更为常见。 这笔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时代没有感染性视网膜炎的HIV患者中观察到的视觉功能障碍的患病率和严重程度。这项工作将通过一项纵向观察研究来完成，该研究将采用各种非侵入性和微创视力测试方法，包括新型视野测试和可以准确测量视网膜位置的多焦点ERG！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，也会形成视网膜棉花斑，这会导致永久性的视网膜和视觉缺陷。我们假设，这些损害的累积效应，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，这是我们所显示的视野丧失的原因。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花斑点。这类研究将使用新的、高度敏感和特定的分子方法，如TaqMan聚合酶链式反应(TaqMan PCR)来确定这些损伤的分子基础。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：即结晶具有强大的抗CMV活性的核苷和核苷酸类似物的能力。将这种晶体注射到患有CMV视网膜炎的眼睛中将导致这些晶体的缓慢溶解和极长效的注射抗CMV药物制剂。

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.