Liu Xin, Wang Huadong, Ma Lin, Ying Min, Liu Qing, Chang Heng, Jin Sen, Yang Fang, Zhu Xutao, Sun Xinghuai, Xu Fuqiang, Liu Haixia
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China; State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, China.
Exp Eye Res. 2022 May;218:109009. doi: 10.1016/j.exer.2022.109009. Epub 2022 Mar 8.
Accumulated clinical evidence has shown that Posner-Schlossman syndrome (PSS) is most likely the result of recurrent human cytomegalovirus (HCMV) infection in the anterior chamber (AC). Establishing an animal model is necessary to investigate the pathogenesis of PSS. In this study, we constructed a mouse model of (PSS) by injecting murine cytomegalovirus (MCMV) into the AC of BALB/c mice. Twenty-five BALB/c mice were divided into 5 groups. Smith strain MCMV expressing enhanced green fluorescent protein (EGFP) was passaged with mouse embryonic fibroblast (MEF). Right eyes in the 4 experiment groups received AC injection of 1 μL of virus solution with concentrations of 10,10,10,10 pfu/mL respectively, and the control group received only PBS. PSS-like signs (mutton-fat keratic precipitates (KP), pupil dilation, IOP elevation and corneal edema) were recorded 0-28 days post-injection (DPI). Sections of eyeballs from another 9 mice harvested on 0,10 and 28 DPI were examined to locate KP and the fluorescence signal of the virus. Reversible PSS-like signs except KP were observed in 20% and 60% mice of 10 and 10 groups while no PSS-like signs in the control and 10 group; 80% in the 10 group with partially unreversible signs till 28DPI. Much More fluorescent signals of virus in the iris and KP were found on 10DPI than 28 DPI, while no fluorescent signals and KP on 0DPI. The extent of PSS-like signs (pupil dilation, IOP elevation and corneal edema) was virus concentration-dependent (Spearman correlation coefficient, r = 0.830, = 0.475, = 0.662, p < 0.0001, <0.05, <0.001, respectively, n = 25). Success rate of PSS model (mice with PSS-like signs) was also virus concentration-dependent (Chi-square trend test, χ = 6.828, df = 1, p < 0.01, n = 25). Our results indicate that AC injection of 1 μL MEF passaged MCMV (Smith strain) of 10-10 pfu/mL in BALB/c mice can be used to construct a mouse model of PSS. MCMV can infect iris tissue and replicate in it and then establish latency. This might account for the recurrent and self-limited nature of PSS.
积累的临床证据表明，波斯纳-施洛斯曼综合征（PSS）很可能是前房（AC）反复感染人巨细胞病毒（HCMV）的结果。建立动物模型对于研究PSS的发病机制很有必要。在本研究中，我们通过向BALB/c小鼠的前房注射鼠巨细胞病毒（MCMV）构建了PSS小鼠模型。25只BALB/c小鼠被分为5组。表达增强型绿色荧光蛋白（EGFP）的史密斯株MCMV在小鼠胚胎成纤维细胞（MEF）中传代。4个实验组的右眼分别接受前房注射1μL浓度为10、10、10、10 pfu/mL的病毒溶液，对照组仅接受磷酸盐缓冲液（PBS）。在注射后0 - 28天（DPI）记录PSS样体征（羊脂状角膜后沉着物（KP）、瞳孔散大、眼压升高和角膜水肿）。对另外9只在0、10和28 DPI处死的小鼠眼球切片进行检查，以定位KP和病毒的荧光信号。10和10组分别有20%和60%的小鼠出现除KP外的可逆性PSS样体征，而对照组和10组未出现PSS样体征；10组有80%出现部分不可逆体征直至28 DPI。在10 DPI时，虹膜和KP中的病毒荧光信号比28 DPI时多得多，而在0 DPI时未发现荧光信号和KP。PSS样体征（瞳孔散大、眼压升高和角膜水肿）的程度呈病毒浓度依赖性（斯皮尔曼相关系数，r分别为0.830、0.475、0.662，p < 0.0001、<0.05、<0.001，n = 25）。PSS模型（出现PSS样体征的小鼠）的成功率也呈病毒浓度依赖性（卡方趋势检验，χ = 6.828，自由度 = 1，p < 0.01，n = 25）。我们的结果表明，向BALB/c小鼠前房注射1μL传代于MEF的10 - 10 pfu/mL MCMV（史密斯株）可用于构建PSS小鼠模型。MCMV可感染虹膜组织并在其中复制，然后建立潜伏状态。这可能解释了PSS的复发和自限性本质。
