Zhang Ming, Xin Hua, Roon Penny, Atherton Sally S
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, 30912, USA.
Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2047-55. doi: 10.1167/iovs.05-0005.
Previous results suggest that retinal neurons are infected early during murine cytomegalovirus (MCMV) infection of the inner retina. The purposes of this study were to identify which retinal neurons are infected and to determine the routes by which MCMV spreads in the retina.
Immunosuppressed (IS) BALB/c mice were inoculated with 5 x 10(3) PFU of MCMV (k181) through the supraciliary route. Injected eyes were collected at several times after inoculation, sectioned, and examined by electron microscopy and by staining for retinal cell antigens and for MCMV early (EA) or late (LA) antigen.
MCMV-infected cells were observed in the choroid and RPE by day 3 after infection (PI) and in the inner retina beginning at day 5 PI. At this time, many horizontal and bipolar cells were MCMV-antigen-positive but only rare MCMV-infected amacrine cells (glycine positive or gamma-aminobutyric acid [GABA] positive) or MCMV-infected ganglion cells (NF positive) were observed in the inner retina. At day 10 PI, most virus-infected cells were glial fibrillary acidic protein (GFAP)- and GABA-positive glia. Virions were observed by electron microscopy in the choroid, RPE, and inner nuclear layer of the retina. Although virions were observed in the endothelium of the retinal vessels and the nearby retinal cells, the endothelial cell lining of the retinal vessels remained intact. Both apoptotic cells and necrotic cells were seen in the inner retina.
In the inner retina, horizontal and bipolar cells were the early (< or = day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Muller cells and within the inner retina horizontally through infected horizontal cells.
先前的研究结果表明，在小鼠巨细胞病毒（MCMV）感染视网膜内层的早期，视网膜神经元就已被感染。本研究的目的是确定哪些视网膜神经元被感染，并确定MCMV在视网膜中传播的途径。
对免疫抑制（IS）的BALB/c小鼠通过睫状体上途径接种5×10³ 空斑形成单位（PFU）的MCMV（k181）。接种后在不同时间收集注射眼，进行切片，并通过电子显微镜以及对视网膜细胞抗原和MCMV早期（EA）或晚期（LA）抗原进行染色来检查。
感染后第3天（PI）在脉络膜和视网膜色素上皮（RPE）中观察到MCMV感染的细胞，从感染后第5天开始在内层视网膜中观察到。此时，许多水平细胞和双极细胞MCMV抗原呈阳性，但在内层视网膜中仅观察到极少数被MCMV感染的无长突细胞（甘氨酸阳性或γ-氨基丁酸[GABA]阳性）或被MCMV感染的神经节细胞（神经丝蛋白[NF]阳性）。感染后第10天，大多数病毒感染的细胞是胶质纤维酸性蛋白（GFAP）和GABA阳性的神经胶质细胞。通过电子显微镜在脉络膜、RPE和视网膜内核层中观察到病毒颗粒。尽管在视网膜血管内皮和附近的视网膜细胞中观察到病毒颗粒，但视网膜血管的内皮细胞内衬保持完整。在内层视网膜中可见凋亡细胞和坏死细胞。
在内层视网膜中，水平细胞和双极细胞是MCMV感染的早期（≤感染后第7天）靶点。病毒从RPE和光感受器层通过受感染的穆勒细胞传播到内层视网膜，并在内层视网膜中通过受感染的水平细胞水平传播。
