Zika virus infects trabecular meshwork and causes trabeculitis and glaucomatous pathology in mouse eyes

Pawan Kumar Singh, Ramesh B. Kasetti, Gulab S. Zode, Anju Goyal, Mark S. Juzych, Ashok Kumar

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Zika virus (ZIKV) infection during pregnancy leads to devastating fetal outcomes, including neurological (microcephaly) and ocular pathologies such as retinal lesions, optic nerve abnormalities, chorioretinal atrophy, and congenital glaucoma. Only clinical case reports have linked ZIKV infection to causing glaucoma, a major blinding eye disease. In the present study, we have investigated the role of ZIKV in glaucoma pathophysiology using in vitro and in vivo experimental models. We showed that human primary trabecular meshwork (Pr. TM) cells, as well as a human GTM3 cell line, were permissive to ZIKV infection. ZIKV induced the transcription of various genes expressing pattern recognition receptors (TLR2, TLR3, and RIG-I), cytokines/chemokines (TNF-α, IL-1β, CCL5, and CXCL10), interferons (IFN-α2, IFN-β1, and IFN-γ), and interferon-stimulated genes (ISG15 and OAS2) in Pr. TM cells. ZIKV infection in IFNAR1-/- and wild-type (WT) mouse eyes resulted in increased intraocular pressure (IOP) and the development of chorioretinal atrophy. Anterior chamber (AC) inoculation of ZIKV caused infectivity in iridocorneal angle and TM, leading to the death of TM cells in the mouse eyes. Moreover, anterior segment tissue of infected eyes exhibited increased expression of inflammatory mediators and interferons. Furthermore, ZIKV infection in IFNAR1-/- mice resulted in retinal ganglion cell (RGC) death and loss, coinciding with optic nerve infectivity and disruption of anterograde axonal transport. Because of similarity in glaucomatous pathologies in our study and other experimental glaucoma models, ZIKV infection can be used to study infectious triggers of glaucoma, currently an understudied area of investigation.

Original languageEnglish
Article numbere00173-19
JournalmSphere
Volume4
Issue number3
DOIs
StatePublished - 1 May 2019

Keywords

  • Axonal transport
  • Eye
  • Glaucoma
  • Intraocular pressure
  • Ocular infection
  • Optic nerve
  • RGC
  • Retina
  • Trabeculitis
  • Zika virus

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