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Yi Li, Chao Shan, Yonju Ha, Fan Xia, Hua Liu, Peiyong Shi, Wenbo Zhang; Zika virus infection induces retinal neuronal and vascular defects during development. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6008. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Zika virus (ZIKV), a mosquito-borne flavivirus, can cause severe eye disease characterized by chorioretinal atrophy, optic neuritis, and blindness in newborns. However, the retinal lesions have not been described explicitly. Here, we developed a mouse model of ZIKVinfection to evaluate its impact on retinal structure.
ZIKV (20 PFU) was injected into the neonatal C57BL/6 mice at Postnatal day (P) 0 subcutaneously. Retinas of ZIKV-infected mice and age-matched controls were collected at P21. Neuronal injury, vascularization, inflammation and gliosis were analyzed by immunostaining with anti-Tuj-1, isolectin B4, anti-CD45 and anti-GFAP in retinal flatmounts. Retinal structural alteration was assessed in retinal sections by DAPIstaining and immunohistochemistry with antibodies against GFAP, glutamine synthetase, CD31, PKCα, calbindin, Dab1, cone-arrestin and rhodopsin.
Compared to control mice, the retinal surface area was much less in ZIKV-treated mice, with dramatically decreased retinal ganglion cells, abnormal vasculature, increased leukocytes, and induced activation of astrocytes and Müller cells. ZIKV-infected retina also displayed evident lack of cells in different retinal layers, including the ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL), resulting in reduced thickness of the whole retina. Moreover, the expression of PKCα, calbindin, Dab1, cone-arrestin and rhodopsin decreased significantly in ZIKV-infected retina, indicating the loss of bipolar cells, horizontal cells, amacrine cells and photoreceptor cells.
We established a novel mouse model of retinal abnormalities associated with ZIKV. These data provide a direct causative link between ZIKV and retinal lesion in vivo. The massive neuronal death, abnormal vasculature and structural disorder in the retina indicate that ZIKV infection can lead to a severe impact on the eye.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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