SARS-CoV-2 Is Able To Cross The Blood-Retinal Barrier And Cause Damage To The Eyes!

COVID-19 News: The human eye is a remarkable organ, equipped with intricate mechanisms to safeguard vision. One such mechanism is the blood-retinal barrier (BRB), which functions similarly to the blood-brain barrier. This barrier is crucial for maintaining ocular health, preventing harmful substances and pathogens from reaching the retina and causing inflammation that could impair vision. However, recent research from the University of Missouri School of Medicine that is covered in this COVID-19 News report has unveiled that SARS-CoV-2, the virus responsible for COVID-19, can breach this protective barrier, posing potential long-term risks to eye health.


A schematic illustration of SARS-CoV-2 ocular tropism via cells lining the blood-retinal barrier (BRB).
Intranasal exposure of SARS-CoV-2 causes ocular tropism and induction of hyperinflammatory response in the retina through BRB infection, whereas ocular exposure does not cause lung infection and moribund illnesses in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. Cells lining the BRB, outer BRB: RPE, and inner BRB: HRvEC are highly permissive to SARS-CoV-2 infection, whereas corneal epithelial cells are comparatively resistant to infection.

Breaking the Barrier: SARS-CoV-2's Invasion
The study, which utilized a humanized ACE2 mice model, demonstrated that SARS-CoV-2 can infect the internal structures of the eyes even if the virus does not enter the body through the ocular surface. The researchers found that when the virus is inhaled, it can travel to protected organs such as the eyes via the bloodstream. This systemic infection allows the virus to cross the BRB by infecting the cells that line it.
 
Lead author of the study, Dr Pawan Kumar Singh, PhD, an assistant professor of ophthalmology at University of Missouri School of Medicine told Thailand Medical News, “The study finding is significant as it enhances our understanding of the long-term effects of SARS-CoV-2 infection. Previously, the focus was on ocular surface exposure, but our findings indicate that SARS-CoV-2 reaches the eye during systemic infection, triggering a hyperinflammatory response in the retina and causing cell death within the BRB. Prolonged presence of viral remnants in the eye elevates the risk of retinal damage and visual impairment.”
 
Ocular Manifestations of COVID-19
The implications of SARS-CoV-2 infection on the eyes are profound. The researchers discovered that the extended presence of the SARS-CoV-2 spike protein in the retina can lead to serious conditions such as retinal microaneurysms, retinal artery and vein occlusion, and vascular leakage. These conditions, if left unchecked, can severely compromise vision.
Dr Singh advised, “For individuals exposed to SARS-CoV-2, it’s advisab le to have an ophthalmologist check for pathological changes in the retina. Even asymptomatic individuals could experience eye damage over time due to COVID-19 complications.”
 
Historically, viruses and bacteria have been known to breach the BRB in immunocompromised individuals, but this research marks the first evidence that SARS-CoV-2 can penetrate this barrier in otherwise healthy individuals, leading to internal eye infections. The study findings are particularly concerning for immunocompromised patients or those with conditions such as hypertension or diabetes, who may face worse outcomes if COVID-19 related ocular symptoms go undiagnosed.
 
Understanding the Mechanisms: Cellular and Molecular Insights
The researchers delved into the cellular and molecular mechanisms by which SARS-CoV-2 infects the eye. They found that SARS-CoV-2 infects cells lining the BRB and induces a hyperinflammatory immune response in the retina via systemic exposure. This hyperinflammatory state can cause significant damage to the retinal cells, which are crucial for maintaining vision.
 
Moreover, the study showed that primary human corneal epithelial cells were relatively resistant to SARS-CoV-2 infection, whereas the cells lining the BRB were highly susceptible. This suggests that while the ocular surface might serve as a physical barrier, the BRB cells, once compromised, could facilitate viral entry and replication.
 
Comorbidities and Increased Susceptibility
The study also highlighted how preexisting conditions like hyperglycemia (high blood sugar) can exacerbate the susceptibility of BRB cells to SARS-CoV-2 infection. Hyperglycemia is known to induce endothelial dysfunction, which compromises the integrity of blood vessels. This breakdown can create a more permissive environment for the virus to breach the barrier.
 
The study found that under hyperglycemic conditions, there was an increased expression of viral entry receptors and a higher rate of SARS-CoV-2-induced cell death in BRB cells. This finding aligns with clinical observations that patients with diabetes experience more severe outcomes when infected with COVID-19.

Long-Term Implications: The Threat of Long COVID
COVID-19 has been associated with long-term health consequences, commonly referred to as long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). This condition affects various organs, including the eyes, and can lead to persistent ocular complications. SARS-CoV-2 has been shown to cause a range of ocular issues, from conjunctivitis and dry eye to more severe conditions like retinal artery and vein occlusion.
 
The study findings demonstrated that prolonged exposure to the SARS-CoV-2 spike protein could cause lasting damage to the retina, including microaneurysms, retinal atrophy, and vein occlusion. These findings underscore the importance of monitoring and addressing long-term ocular health in COVID-19 patients.
 
SARS-CoV-2 and the Eye: A Broader Perspective
The relationship between SARS-CoV-2 and ocular health is complex. The eye, being an immune-privileged organ, can become a sanctuary for viral replication, posing a challenge for both diagnosis and treatment. The study’s findings suggest that the virus can cross the BRB, similar to how it crosses the blood-brain barrier, leading to potential neuroinvasion and ocular complications.
 
The researchers observed that while ocular exposure to the virus did not result in systemic illness, intranasal exposure led to viral presence in the eye and a significant inflammatory response in the retina. This indicates that systemic exposure to the virus, rather than direct ocular exposure, poses a greater risk for ocular complications.
 
The Path Forward: Preventive and Therapeutic Strategies
The insights gained from this study are crucial for developing strategies to prevent and treat COVID-19-related ocular complications. Understanding the mechanisms of SARS-CoV-2 ocular tropism and the role of the BRB in viral infection can inform the creation of targeted therapies to protect and preserve vision in affected individuals.
 
Dr Singh emphasized the need for further research to elucidate the long-term consequences of SARS-CoV-2 infection on ocular health. “Our main goal is to better understand the cellular and molecular mechanisms of how this virus breaches the blood-retinal barrier and the associated pathological consequences,” he said. “This study data will be instrumental in developing therapies to prevent and treat COVID-19-induced eye complications before a patient’s vision is compromised.”
 
Conclusion: Vigilance in Eye Health During the Pandemic
The study findings highlight a critical yet often overlooked aspect of COVID-19's impact on health—the potential for significant and lasting damage to vision. As the pandemic continues, it is essential for both healthcare providers and patients to remain vigilant about ocular health. Regular eye examinations and awareness of potential symptoms can help detect and address complications early, potentially preserving vision and improving quality of life for those affected by COVID-19.
 
The study findings were published in the peer revied journal: PLOS Pathogens.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012156
 
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