Viral retinopathy in experimental models of zika infection

Zhenyang Zhao, Matthew Yang, Sasha R. Azar, Lynn Soong, Scott C. Weaver, Jiaren Sun, Yan Chen, Shannan L. Rossi, Jiyang Cai

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

PURPOSE. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)4075-4085
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number10
DOIs
StatePublished - Aug 1 2017

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Keywords

  • Axl
  • Müller cell
  • RPE
  • Tyro 3
  • Zika virus

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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