Zhao Zhenyang, Yang Matthew, Azar Sasha R, Soong Lynn, Weaver Scott C, Sun Jiaren, Chen Yan, Rossi Shannan L, Cai Jiyang
Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, Texas, United States.
Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, United States.
Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):4355–4365. doi: 10.1167/iovs.17-22016.
Emerging evidence has shown that both congenital and adult Zika virus (ZIKV) infection can cause eye diseases. The goals of the current study were to explore mechanisms and pathophysiology of ZIKV-induced eye defects.
Wild-type or A129 interferon type I receptor-deficient mice were infected by either FSS13025 or Mex1-7 strain of ZIKV. Retinal histopathology was measured at different time points after infection. The presence of viral RNA and protein in the retina was determined by in situ hybridization and immunofluorescence staining, respectively. Growth curves of ZIKV in permissive retinal cells were assessed in cultured retinal pigment epithelial (RPE) and Müller glial cells.
ZIKV-infected mice developed a spectrum of ocular pathologies that affected multiple layers of the retina. A primary target of ZIKV in the eye was Müller glial cells, which displayed decreased neurotrophic function and increased expression of proinflammatory cytokines after infection. ZIKV also infected RPE; and both the RPE and Müller cells expressed viral entry receptors TYRO3 and AXL. Retinitis, focal retinal degeneration, and ganglion cell loss were observed after the clearance of viral particles.
Our data suggest that ZIKV can infect infant eyes with immature blood-retinal barrier and cause structural damages to the retina. The ocular findings in microcephalic infants may not be solely caused by ZIKV-induced impairment of neurodevelopment.
新出现的证据表明，先天性和成人寨卡病毒（ZIKV）感染均可导致眼部疾病。本研究的目的是探讨ZIKV诱导眼部缺陷的机制和病理生理学。
野生型或I型干扰素受体缺陷型A129小鼠分别感染ZIKV的FSS13025或Mex1-7毒株。在感染后的不同时间点测量视网膜组织病理学。分别通过原位杂交和免疫荧光染色确定视网膜中病毒RNA和蛋白质的存在。在培养的视网膜色素上皮（RPE）细胞和 Müller 胶质细胞中评估ZIKV在允许性视网膜细胞中的生长曲线。
ZIKV感染的小鼠出现了一系列影响视网膜多层的眼部病变。ZIKV在眼中的主要靶细胞是Müller胶质细胞，感染后其神经营养功能下降，促炎细胞因子表达增加。ZIKV也感染RPE；RPE细胞和Müller细胞均表达病毒进入受体TYRO3和AXL。病毒颗粒清除后观察到视网膜炎、局灶性视网膜变性和神经节细胞丢失。
我们的数据表明，ZIKV可感染血视网膜屏障不成熟的婴儿眼睛，并对视网膜造成结构损伤。小头畸形婴儿的眼部表现可能并非完全由ZIKV诱导的神经发育受损所致。
