Abstract
Purpose :
SARS-CoV-2 has shown ocular tropism with pervasive ocular manifestations in COVID-19 patients. However, the role of eyes in SARS-CoV-2 transmission, tropism, and associated pathology remains unknown. In this study, we aimed to investigate whether the ocular tropism of SARS-CoV-2 is via ocular surface exposure or systemic routes and the role of the eye in viral transmission and its long-term consequences.
Methods :
K18-hACE2 mice were challenged with SARS-CoV-2 via inhalation (IN) or ocular (OC) exposure for 7, 14, and 21 days. At respective endpoints, eyes were enucleated, and the viral burden was assessed by qPCR and immunofluorescence staining. For in vitro studies, cells lining the blood-retinal barrier (BRB), primary human retinal pigmented epithelium (RPE), primary human retinal vascular endothelial cells (HRvEC), and primary human corneal epithelial cells (HCEC), primary human trabecular meshwork cells (HTMC) were infected with SARS-CoV-2 for 48, 72, and 96h in normal and hyperglycemic conditions. The viral burden, viral entry receptor expression, and innate immune response were measured using IFA and qPCR. The BRB cell death was measured using the TUNEL assay.
Results :
SARS-CoV-2 exposure via IN and OC routes demonstrated the presence of viral spike protein in various ocular tissues in K18-hACE2 mice. However, the OC exposure failed to transmit the virus to the lungs or establish moribund illness despite the extended presence of viral remnants in various ocular tissues. Furthermore, the IN exposure induced a hyperinflammatory immune response in the retina, indicating a systemic permeation of the virus. Our results confirmed that cells lining the BRB, outer BRB, RPE, inner BRB, and HRvEC cells are highly permissive to SARS-CoV-2 infection. Unexpectedly, HCECs were found comparatively resistant to SARS-CoV-2 infection. HTMC cells showed permissivity towards the virus, indicating viral tropism to the anterior segment. SARS-CoV-2 induced cell death and an innate antiviral response in BRB cells. Moreover, hyperglycemia enhanced the susceptibility of BRB to viral infection and cell death.
Conclusions :
Our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina and induce retinal inflammation via systemic exposures.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.