PATHOGENESIS OF CMV RETINITIS

巨细胞病毒（CMV）视网膜炎是最常见的眼科疾病 艾滋病患者的机会性感染。虽然临床和 艾滋病相关CMV视网膜炎的组织病理学特征已经 虽然被广泛描述，但这种疾病的发病机制尚不清楚。 明白我们的建议探讨了CMV视网膜炎的发病机制， 我们实验室开发的一种新的小鼠疾病模型。我们 假设鼠CMV（MCMV）视网膜炎具有类似于 艾滋病相关的CMV视网膜炎将在成年C57 BL/6小鼠中发展， 小鼠获得性免疫缺陷综合征（MAIDS）， 由鼠逆转录病毒混合物引起免疫抑制性疾病 类似于HIV-1导致的人类艾滋病我们预测这种动物 巨细胞病毒视网膜炎模型可用于解决几个基本问题， 与发病机制相关的临床相关问题， 逆转录病毒诱导的CMV视网膜炎的治疗 免疫抑制我们将评估这一假设和预测， 首先进行一系列旨在表征 疾病的演变。具体来说，我们将探讨组织病理学 和病毒学特征的视网膜炎在不同阶段的MAIDS，检查 与疾病相关的视网膜炎症的性质，以及 鉴定对MCMV感染敏感的视网膜细胞。 其他研究将集中在免疫调节剂对免疫功能的影响。 视网膜炎的克里思和严重程度。这些将包括艾滋病引起的 免疫抑制、特异性免疫细胞亚群的耗竭和过继性 病毒特异性效应物的转移和抗逆转录病毒的作用 已知会导致人类骨髓毒性的药物。最后我们 将研究更昔洛韦对MCMV视网膜炎的作用， 视网膜的细胞，作为病毒的储存库， 用这种抗病毒药物治疗。本研究项目的长期目标是 是为了确定在进化过程中发生的致病事件， 逆转录病毒感染导致免疫抑制的CMV视网膜炎， 可以开发更创新的治疗方法， 治疗这种严重威胁视力的疾病

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.