VIROLOGIC AND IMMUNOLOGIC STUDIES MURINE CMV RETINITIS

鼠 CMV 视网膜炎的病毒学和免疫学研究

• 批准号: 6650291
• 负责人: SALLY S ATHERTON
• 金额: $ 25.11万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650291
• 关键词: T lymphocyte; apoptosis; artificial immunosuppression; biomarker; blood aqueous barrier; cytomegalovirus; cytomegalovirus retinitis; disease /disorder model; host organism interaction; laboratory mouse; latent virus infection; passive immunization; pathologic process; regulatory gene; retinal pigment epithelium; tumor necrosis factor alpha; virus infection mechanism; virus replication

DESCRIPTION (Applicant's Description): Even though much known about the course and treatment of CMV retinitis in immunosuppressed human patients, many aspects of the pathogenesis of CMV retinitis remain to be deciphered. Understanding the pathogenesis of CMV retinitis continues to be an important area of investigation since even though the incidence of new cases of CMV retinitis decreased in patients on highly active antiretroviral therapy (HAART) and several antivirals with anti-CMV activity are widely available, the number of new cases of CMV retinitis has begun to slowly increase again at many centers. The studies proposed in this application will use the BALB/c mouse model of MCMV retinitis and will focus on those aspects of retinitis in the mouse that appear to be relevant to understanding the pathogenesis of CMV retinitis in human patients - latency and reactivation in the eye, the role of the blood-retinal barrier (BRB) and whether intravenously injected virus-infected cells enter and infect the retina, and finally, the role of infected RPE in causing apoptosis of apparently uninfected retinal cells. The first Specific Aim is to define the site(s) of latency in the eye and whether the route that is used for ocular injection plays a role in determining the sites at which MCMV becomes latent. The second Specific Aim is to determine if MCMV can spread to and replicate in the retina of immunosuppressed mice following disruption of the BRB and intravenous injection of MCMV-infected mononuclear cells or MCMV. The third Specific Aim is to determine the mechanism by which infection of the RPE results in apoptosis of the overlying retina. By using the mouse model to provide new information about how MCMV causes infection of the retina, the results of these studies may provide new insight into the mechanisms of CMV infection of the retina in human patients, which, in turn, might lead to new therapies for preventing infection or reducing its harmful effects.

描述（申请人的描述）：尽管对课程了解很多 和治疗免疫抑制的人类患者中的CMV视网膜炎， CMV视网膜炎的发病机制仍有待阐明。了解 CMV视网膜炎的发病机制仍然是一个重要的领域， 调查以来，即使新的CMV视网膜炎病例的发病率 在接受高效抗逆转录病毒治疗（HAART）的患者中减少， 几种具有抗CMV活性的抗病毒药物是广泛可用的， CMV视网膜炎的新病例在许多中心又开始缓慢增加。 本申请中提出的研究将使用BALB/c小鼠模型， MCMV视网膜炎，并将集中在这些方面的视网膜炎，在小鼠， 似乎与了解CMV视网膜炎的发病机制有关， 人类患者-眼睛中的潜伏期和再激活， 血视网膜屏障（BRB）和静脉注射的病毒是否感染 细胞进入并感染视网膜，最后，被感染的RPE在 导致明显未感染的视网膜细胞凋亡。第一特定 目的是定义眼睛中的延迟部位，以及 用于眼部注射，在确定 MCMV变为潜伏性。第二个具体目标是确定MCMV是否可以传播 并在免疫抑制小鼠的视网膜中复制， BRB和静脉注射MCMV感染的单核细胞或MCMV。 第三个具体目标是确定感染的机制， RPE导致上覆视网膜的细胞凋亡。通过使用小鼠模型， 提供了关于MCMV如何引起视网膜感染的新信息， 这些研究结果可能为CMV的机制提供新的见解 感染的视网膜在人类患者，这反过来，可能会导致新的 预防感染或减少其有害影响的治疗。