Dix Richard D, Cousins Scott W
Department of Ophthalmology, Jones Eye Institute, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA.
Curr Eye Res. 2004 Aug-Sep;29(2-3):173-80. doi: 10.1080/02713680490504876.
To correlate tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) synthesis with histopathologic disease and virus replication within murine cytomegalovirus (MCMV)-infected eyes during progression of murine acquired immunodeficiency syndrome (MAIDS).
Groups of normal mice and mice with MAIDS of 2-weeks (MAIDS-2), 4-weeks (MAIDS-4), and 12-weeks (MAIDS-12) duration were infected uniocularly with MCMV by subretinal MCMV injection. MCMV-inoculated eyes from all mice were subjected to histopathologic analysis, quantitative plaque assay, or cytometric bead array analysis for quantification of TNF-alpha and IFN-gamma.
Whereas MCMV-inoculated eyes of normal, MAIDS-2, and MAIDS-4 mice were resistant to MCMV retinitis, all MCMV-inoculated eyes of MAIDS-12 mice developed retinitis. Surprisingly, MCMV-inoculated eyes of MAIDS-4 mice without retinitis harbored high amounts of infectious virus at a level equivalent to that of MCMV-inoculated eyes of MAIDS-12 mice that developed retinitis. Intraocular TNF-alpha levels were consistently approximately 50% greater in MCMV-inoculated eyes of MAIDS-12 mice when compared with TNF-alpha levels of normal, MAIDS-2, and MAIDS-4 mice. In contrast, intraocular INF-gamma levels within MCMV-inoculated eyes progressively declined as animals became susceptible to retinitis.
An inverse relationship exists between TNF-alpha and INF-gamma production within MCMV-inoculated eyes during MAIDS evolution that is characterized by an increase in intraocular TNF-alpha levels and a concomitant decrease in intraocular INF-gamma levels. Susceptibility of MCMV-inoculated eyes to virus replication and development of necrotizing retinitis are independent events with susceptibility to MCMV replication preceding susceptibility to MCMV retinitis by several weeks. Time of Th1/Th2 shift in cytokine profile appears to be a crucial event in the pathogenesis of MAIDS-related MCMV retinitis.
在小鼠获得性免疫缺陷综合征（MAIDS）进展过程中，将肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的合成与组织病理学疾病以及鼠巨细胞病毒（MCMV）感染眼内的病毒复制相关联。
将正常小鼠以及病程为2周（MAIDS-2）、4周（MAIDS-4）和12周（MAIDS-12）的MAIDS小鼠分组，通过视网膜下注射MCMV单眼感染。对所有小鼠接种MCMV的眼睛进行组织病理学分析、定量空斑试验或细胞计数珠阵列分析，以定量TNF-α和IFN-γ。
正常小鼠、MAIDS-2小鼠和MAIDS-4小鼠接种MCMV的眼睛对MCMV视网膜炎具有抗性，而MAIDS-12小鼠接种MCMV的所有眼睛均发生视网膜炎。令人惊讶的是，未发生视网膜炎的MAIDS-4小鼠接种MCMV的眼睛携带大量感染性病毒，其水平与发生视网膜炎的MAIDS-12小鼠接种MCMV的眼睛相当。与正常小鼠、MAIDS-2小鼠和MAIDS-4小鼠的TNF-α水平相比，MAIDS-12小鼠接种MCMV的眼睛内TNF-α水平始终高出约50%。相反，随着动物对视网膜炎易感，接种MCMV的眼睛内眼内IFN-γ水平逐渐下降。
在MAIDS演变过程中，接种MCMV的眼睛内TNF-α和IFN-γ产生之间存在负相关关系，其特征是眼内TNF-α水平升高，同时眼内IFN-γ水平降低。接种MCMV的眼睛对病毒复制的易感性以及坏死性视网膜炎的发生是独立事件，对MCMV复制的易感性比对视网膜炎的易感性提前数周。细胞因子谱中Th1/Th2转变的时间似乎是MAIDS相关MCMV视网膜炎发病机制中的关键事件。
