new symptom could lead to blindness, study finds

While Covid-19 is usually associated with infection of the lungs, heart and other vital organs, a growing body of evidence suggests infection can also impact the eye.

About 1 in 10 people exposed to Covid-19 have at least one eye problem, such as dryness, redness, blurred vision and sensitivity to light.

Conjunctivitis, or “pink eye”, can also appear in the early stages of infection, suggesting it could be one of the earliest markers of Covid-19 infection.

Given the direct connection between the eye and the brain via the optic nerve, infection of the retina could open a window to the rest of the brain.

Idea about possible consequences

Thanks to a study published by researchers from the Max Planck Institute for Molecular Biomedicine in Germany, we can now have a better idea of ​​how SARS-CoV-2 infects cells in the eye and the possible consequences on the rest of the nervous system.

To track changes in the eye after exposure to Covid-19, Menuchin-Lasowski et al. used retinal organoids, small three-dimensional tissue cultures resembling human retinas.

These stem cell-derived tissues contain most cell types found in the retina, including photoreceptors and amacrine and horizontal supporting cells, properly organized into a layered structure.

As these cells grew and reached maturity, the researchers exposed the retinal organoids to the SARS-CoV-2 virus. To their surprise, Menuchin-Lasowski et al. found that SARS-CoV-2 not only infects cells, but also replicates.

This was evident by the production of viral plaques in cells exposed to the virus. The amount of viral plaque increased dramatically during the first 24 hours and almost doubled after another 24 hours.

Observation similar pattern of Covid-19 infection

Interestingly, after 72 hours the amount of plaque decreased back to the levels detected in the first 24 hours. Previous studies have observed a similar pattern of Covid-19 infection in human brain organoids.

How are cells infected in the first place? Although viral transmission through the eye has not been well described, SARS-CoV-2 can penetrate the mucous membranes that line several organs, including the respiratory system, as well as the surface of the eye and the eyelids.

When a droplet containing the virus lands on the surface of the eye, SARS-CoV-2 likely travels through the mucous membrane into the inner eye cavity before finally reaching the retina which lies at the very bottom. bottom of the eye.

Relatively low expression of the ACE-2 receptor used by SARS-CoV-2 to enter cells has been detected in the eye. Strikingly, Menuchin-Lasowski et al. found that blocking this receptor could prevent infection of retinal organoids, suggesting that ACE-2 may be the main mechanism of eye infection despite low levels of expression.

Eye cells vulnerable to Covid-19 infection

Which retinal structures were directly infected? Retinal ganglion cells appear to be the most vulnerable to Covid-19 infection. retinal ganglion cells are neural cells that cover the inner surface of the retina.

They receive visual information detected by photoreceptors and transmitted through horizontal and amacrine cells. The ganglion cell axons then bundle together to form the optic nerve, which connects directly to the visual areas of the brain.

Widespread damage to these cells can significantly impair vision. New studies show that degeneration of retinal ganglion cells and/or photoreceptors by Covid-19 can lead to virtual permanent impairments or blindness.

About 40% of SARS-CoV-2 infected cells in this survey were retinal ganglion cells, compared to a small percentage of photoreceptors and even fewer bipolar and amacrine cells. Although located in the inner layers of the retina, the ganglion cells seem particularly susceptible to infection.

Reports of conjunctivitis and other eye problems linked to Covid-19 signal that inflammatory damage is occurring in the eye. It is possible that the retinal lesion is a consequence of vascular dysfunction around the eye related to infection of the epithelial cells lining the blood vessels.

Retinal ganglion cell damage

Menuchin-Lasowski et al. also speculates that infected retinal ganglion cells may activate inflammatory signal pathways that damage nearby cells. In fact, common retinal lesions generated by Covid-19, such as optic nerve swelling and ganglion cell layer damage, appear to be related to retinal ganglion cell damage.

Menuchin-Lasowski et al., for example, reported that infection of retinal organoids increased the expression of several inflammatory genes, consistent with previous findings that SARS-CoV-2 induces a robust immune response.

The cytokine IL-33, in particular, was significantly upregulated. The prevalence of IL-33 in the blood of people exposed to Covid-19 has been shown to correlate with the severity of the disease. The enhanced IL-33 was also accompanied by increased expression of NLRP1, an inflammatory protein implicated in degenerative eye diseases that cause irreversible blindness.

SARS-CoV-2 an inflammatory disease?

Interestingly, genes associated with DNA repair, recombination and metabolism were significantly down-regulated, which may explain why symptoms related to Covid-19 infection continue to persist long after infection. initial infection. These findings only add to the growing body of evidence that SARS-CoV-2 is largely an inflammatory disease.

Previously, the impact of Covid-19 on the eye had not been well understood. “However, our current retinal-organoid study shows that Sars-CoV-2 infection can have direct pathological consequences for retinal ganglion cells, even though visual impairment is not common in patients with Covid-19,” said Dr. Thomas Rauen, co-lead author of this study and project group leader of the “Brain Organoids: Alternatives to Animal Testing” white paper.

These findings may help us better understand the pathology of Covid-19. Not only of the eye but also of the rest of the nervous system.

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