Abstract
Purpose :
Glaucoma is classically viewed as a genetic and age-related disease and has rarely been associated with congenital infections. However, during the recent epidemics in Brazil, Zika virus (ZIKV) infection during pregnancy has been linked to cause glaucoma in infants. The aim of this study is to investigate the pathobiology of ZIKV induced glaucoma.
Methods :
C57BL/6 wild type (WT) and IFNAR1-/- adult mice and pregnant dams were challenged with ZIKV strain PRVABC59 by anterior chamber (AC) and subcutaneous (s.c.) injections respectively. Intraocular pressure (IOP) was recorded at various time-points post-ZIKV infection. Trabecular meshwork (TM), retinal ganglion cells (RGCs) infectivity and cell death were assessed using immunofluorescence and TUNEL staining respectively. Axonal transport was measured by intravitreal injection of cholera toxin subunit B (CTB) and optic nerve imaging. For in vitro studies, human primary TM cells (HTMC) and GTM3 cell line were challenged with ZIKV at multiplicity of infection (MOI) 1 followed by measurements of innate antiviral responses using qPCR
Results :
ZIKV infection caused increased IOP and the development of chorioretinal atrophy in both WT and IFNAR1-/- mouse eyes. AC inoculation of ZIKV caused infectivity in iridocorneal angle and TM, leading to the death of TM cells in the mouse eyes. ZIKV challenge resulted into RGC death and loss in the infected mice and neonate pups born from infected dams. ZIKV infection in IFANR1-/- mice caused optic nerve infectivity and disruption of anterograde axonal transport. ZIKV infection in mice induced autophagy in the anterior segment tissue, and autophagy inhibition using an FDA approved drug- Hydroxychloroquine (HCQ) attenuates ZIKV induced ocular pathology. HTMC and GTM3 cells were found to be permissive to ZIKV and evoked an innate antiviral response.
Conclusions :
Our study for the first time showed experimental evidence of ZIKV induced glaucoma. Because of the 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.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.