Study: Virus that causes COVID-19 can penetrate blood-retinal barrier and may damage vision

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The blood-retinal barrier is designed to protect an individual’s vision from infections by preventing microbial pathogens from reaching the retina where they could trigger an inflammatory response with potential vision loss. A team of researchers at the University of Missouri School of Medicine has found the virus that causes COVID-19 can breach this protective retinal barrier with potential long-term consequences in the eye.

The team is led by Pawan Kumar Singh, PhD, an assistant professor of ophthalmology. They have researched ways to prevent and treat ocular infectious diseases.

According to a University of Missouri news release, by using a humanized ACE2 mice model, the researchers found that SARS-CoV-2, the virus that causes COVID-19, can infect the inside of the eyes even when the virus doesn’t enter the body through the surface of the eyes. Instead, they found that when viruses enter the body through inhalation, it not only infects organs like lungs, but also reaches highly protected organs like eyes through the blood-retinal barrier by infecting the cells lining this barrier.¹

Singh said the finding is important as researchers increase their understanding of the long-term effects of SARS-CoV-2 infection.

“Earlier, researchers were primarily focused on the ocular surface exposure of the virus,” he said in the news release. “However, our findings reveal that SARS-CoV-2 not only reaches the eye during systemic infection but induces a hyperinflammatory response in the retina and causes cell death in the blood-retinal barrier.”

Singh pointed out the longer viral remnants remain in the eye, the risk of damage to the retina and visual function increases. He also discovered that extended presence of SARS-CoV-2 spike antigen can cause retinal microaneurysm, retinal artery and vein occlusion, and vascular leakage.

“For those who have been diagnosed with COVID-19, we recommend you ask your ophthalmologist to check for signs of pathological changes to the retina,” Singh said in the release. “Even those who were asymptomatic could suffer from damage in the eyes over time because of COVID-19 associated complications.”

According to the news release, while viruses and bacteria have been found to breach the blood-retinal-barrier in immunocompromised people, this research is the first to suggest that the virus that causes COVID-19 could breach the barrier even in otherwise healthy individuals, leading to an infection that manifests inside the eye itself. Immunocompromised patients or those with hypertension or diabetes may experience worse outcomes if they remain undiagnosed for COVID-19 associated ocular symptoms.¹

“Now that we know the risk of COVID-19 to the retina, our goal is to better understand the cellular and molecular mechanisms of how this virus breaches the blood-retinal barrier and associated pathological consequences in hopes of informing development of therapies to prevent and treat COVID-19 induced eye complications before a patient’s vision is compromised,” Singh said.

The study, titled “SARS-CoV-2 infects cells lining the blood-retinal barrier and includes a hyperinflammatory immune response in the retina via systematic exposure,’ was published recently in PLOS Pathogens.

“Our study demonstrated that the ocular infection by SARS-CoV-2 occurs during both OC and IN exposures,” the researchers wrote. “The IN route can disseminate the virus to the eye; in contrast, the OC exposure fails to transmit the virus to distal organs or cause lethal infections.”

Moreover, the researchers noted the induction of hyperinflammatory retinal responses in IN-exposed groups and the increased permissivity of cells lining the blood-retinal barrier (RPE and HRvEC) indicates a systemic permeation of the virus through the blood-retinal barrier.

“BRB cells express receptors for viral entry and are highly prone to SARS-CoV-2-induced cell death,” the researchers added. “Moreover, our data demonstrated that the SARS-CoV-2 ocular manifestations are exacerbated by comorbidities.”

The researchers noted in the study additional research is required to assert the long-term consequences of SARS-CoV-2 live infection on retinal health.

“Conclusively, our study demonstrates the critical role of BRB in SARS-CoV-2 infection and ocular tropism, which will help in designing therapeutic strategies to treat or prevent COVID-19-mediated ocular complications,” they concluded.

Singh’s University of Missouri School of Medicine research team included

Vaishnavi Balendiran, MD, vitreoretinal surgery fellow; Monu Monu and Faraz Ahmad, post-doctoral fellows in the Department of Ophthalmology; and Rachel M. Olson, PhD, chief scientific officer, Laboratory for Infectious Disease Research at the College of Veterinary Medicine.

This research was supported through funding from the University of Missouri and a National Institutes of Health/National Eye Institute grant R01EY032495.

References

1. COVID-19 Virus Could Damage Vision. medicine.missouri.edu. Published May 14, 2024. Accessed May 14, 2024. https://medicine.missouri.edu/news/covid-19-virus-could-damage-vision‌

2. Monu Monu, Ahmad F, Olson RM, Vaishnavi Balendiran, Pawan Kumar Singh. SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure. PLOS pathogens. 2024;20(4):e1012156-e1012156. doi:https://doi.org/10.1371/journal.ppat.1012156