PATHOGENESIS OF CMV RETINITIS

巨细胞病毒视网膜炎的发病机制

• 批准号: 2164528
• 负责人: Richard D Dix
• 金额: $ 19.76万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2164528
• 关键词: AIDS; Herpesviridae disease; acquired immunodeficiency; antiviral agents; cellular pathology; cytomegalovirus; disease /disorder classification; disease /disorder model; eye infections; eye pharmacology; ganciclovir; histopathology; immunomodulators; immunosuppression; laboratory mouse; opportunistic infections; retina; retinitis

Cytomegalovirus (CMV) retinitis is the most frequent ophthalmic opportunistic infection in patients with AIDS. Although the clinical and histopathologic features of AIDS-related CMV retinitis have been extensively described, the pathogenesis of this disease is poorly understood. Our proposal explores the pathogenesis of CMV retinitis is terms of a new mouse model of the disease developed in our laboratory. We hypothesize that murine CMV (MCMV) retinitis with features similar to AIDS-related CMV retinitis will develop in adult C57BL/6 mice suffering from murine acquired immune deficiency syndrome (MAIDS), an immunosuppressive disorder produced by a mixture of murine retroviruses that parallels HIV-l-induced AIDS in humans. We predict that this animal model of CMV retinitis can be used to address several fundamental, clinically-relevant questions that relate to the pathogenesis and treatment of CMV retinitis in a setting of retrovirus-induced immunosuppression. We will evaluate this hypothesis and prediction by first performing a series of experiments designed to characterize the evolution of disease. Specifically, we will explore the histopathologic and virologic features of retinitis at various stages of MAIDS, examine the nature of the retinal inflammation associated with the disease, and identify the cell(s) of the retina that are susceptible to MCMV infection. Additional studies will focus on the effect of immunomodulators on the tempo and severity of retinitis. These will include MAIDS-induced immunosuppression, depletion of specific immune cell subsets and adoptive transfer of virus-specific effectors, and the effect of antiretrovirus drugs that are known to induce bone marrow toxicity in humans. Finally, we will investigate the effect of ganciclovir on MCMV retinitis and identify the cell(s) of the retina that serve as reservoirs for virus during treatment with this antiviral. The long term goal of this research project is to define the pathogenetic events that occur during the evolution of CMV retinitis in persons immunosuppressed by retrovirus infection, so that more innovative therapeutic approaches can be developed for improved treatment of this devastating sight-threatening disease.

巨细胞病毒（CMV）视网膜炎是最常见的眼科 艾滋病患者的机会感染。虽然临床和 与艾滋病相关的CMV视网膜炎的组织病理学特征已经 广泛描述了该疾病的发病机理 理解。我们的建议探讨了CMV视网膜炎的发病机理是 我们实验室开发的新小鼠模型的术语。我们 假设鼠CMV（MCMV）视网膜炎具有类似的特征 与AIDS相关的CMV视网膜炎将在成年C57BL/6小鼠中发展 从鼠获得免疫缺陷综合症（女仆）中 鼠逆转录病毒混合产生的免疫抑制症 这与HIV-L诱导的辅助工具相似。我们预测这种动物 CMV视网膜炎模型可用于解决几种基本的， 与发病机理有关的临床问题和 在逆转录病毒诱导的环境中治疗CMV视网膜炎 免疫抑制。我们将通过 首先执行一系列旨在表征的实验 疾病的进化。具体来说，我们将探索组织病理学 在女仆的各个阶段的视网膜炎的病毒学特征，检查 与疾病相关的视网膜炎症的性质， 识别易受MCMV感染的视网膜细胞。 其他研究将侧重于免疫调节剂对 视网膜炎的速度和严重程度。这些将包括女仆引起的 免疫抑制，特异性免疫细胞子集的耗竭和收养 病毒特异性效应子的转移和抗逆转录病毒的作用 已知会诱导人类骨髓毒性的药物。最后，我们 将研究Ganciclovir对MCMV视网膜炎的影响并鉴定 视网膜的细胞作为病毒的储藏 用这种抗病毒治疗。该研究项目的长期目标 是定义在演变中发生的致病事件 通过逆转录病毒感染免疫抑制的人的CMV视网膜炎，以便 可以开发更具创新的治疗方法来改进 治疗这种毁灭性的视力危及疾病。