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Medical Scientists Find ACE2 in Eye Tissue, Leading to Concern that the Eyes Are a Port of Entry for SARS-CoV-2 and COVID-19 Infection

Sun May 10 2020 9:13 pm
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Some patients suffering from Coronavirus COVID-19 have exhibited conjunctivitis, which raised concern of a group of medical scientists that decided to examine the eyes of patients that died and tested positive for COVID-19, and compare the eye tissue to healthy patients who were undergoing photorefractive keratectomy for the treatment of mild to moderate myopia or myopic astigmatism. The scientists published their study as a preprint before certification by peer review on biorxiv.

The medical scientists (affiliated with Johns Hopkins University School of Medicine and State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University in Guangzhou, China) performed an immunohistochemical analysis of eye tissue for the purpose of determining whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry or infection.

All of the eye specimens undergoing immunohistochemical analysis with staining revealed expression of ACE2 in …

1) the conjunctiva (the tissue that lines the eyelids and the white of eye);

2) the cornea (the transparent tissue that covers the iris (color part of eye), pupil (the black hole in the center of the iris that responds to light) and anterior chamber of the eye, and interfaces with the environment (air, water); and

3) the limbus (the border of the cornea and the white of the eye or sclera).

ACE2 expression was especially prominent with staining in the superficial conjunctival and corneal epithelial surface — areas the scientist noted are highly exposed to aerosol droplet contact.

Surgical conjunctival specimens from healthy patients (undergoing photorefractive keratectomy for the treatment of mild to moderate myopia or myopic astigmatism) also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria (the transparent and thickest layer of the cornea consisting of collagen fibrils that only direct light toward the retina).

All eye and conjunctival specimens also expressed TMPRSS2 (known as the enzyme Transmembrane protease, serine 2). Finally, western blot (a widely used molecular biology test) for analysis of protein lysates (prepared disintegrated proteins for study) from human corneal epithelium obtained during refractive surgery, confirmed expression of ACE2 and TMPRSS2.

The scientists concluded that the results of the study indicate that ocular surface cells, including conjunctiva, are susceptible to infection by SARS-CoV-2 (the virus that causes COVID-19 infection), and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this coronavirus.

The scientists also mentioned that various investigators have detected the presence of SARS-CoV-2 in eye tears. Additionally the scientists cited a study that detected the presence of virus in ocular swabs, indicating virus in the eye as long as 27 days after initial symptoms, even when there was no longer any virus detected in nasal swabs.

The scientists said the results highlight the importance of safety practices, including the wearing of complete face masks and ocular contact precautions in preventing the spread of COVID-19 disease.

The scientists remarked that the surface of the eyes could potentially serve as a portal of entry by exposure to aerosolized drops from infected people and hand-eye contact from contaminated hands.

The study cited sources reporting that nasal epithelial cells and bronchial secretory cells are already known to possess the key factors for cellular susceptibility to SARS-CoV-2.

ACE2 serves as the key cell surface receptor for SARS-CoV-2 that binds the viral spike protein that emanates from the coronavirus. Also, TMPRSS2 is known to be an important cell surface-associated protease that allows viral entry into the cell and infection following binding of the viral spike protein to ACE2. The healthy, primary function of ACE2 in the human body is to counterbalance ACE. Regarding blood pressure regulation, ACE converts angiotensin I to angiotensin II and indirectly increases blood pressure by causing blood vessels to constrict (vasoconstriction). Hypertension or high blood pressure related to this process is treated with ACE inhibitors and ARBs (Angiotensin II receptors blockers).

Besides locations at the nasal epithelium and bronchial secretory cells, ACE2 or Angiotensin-converting enzyme 2 is known to be an enzyme attached to the outer surface (cell membranes) of cells in the lungs, arteries, heart, kidneys, and intestines (or most organs). Following a complicated set of chemical reactions affecting hormones involving ACE, angiotensin I and angiotensin II; the ACE2 enzyme ultimately metabolizes angiotensin II, which would otherwise cause vasoconstriction and high blood pressure.

So ACE2 is good for preventing high blood pressure, but it is bad because the SARS-CoV-2 “knows” how to use ACE2 to infect cells. Since scientists have now found ACE2 in eye tissue, this leads to concern that SARS-CoV-2 can infect by contact with eyes, as well as the nose and lungs.

The scientists also noted that infection of ocular surface cells could lead to understanding that the eye is an important carrier, with ocular virus shedding constituting a significant mechanism for infection of other individuals.

SOURCE: Lingli Zhoua, Zhenhua Xua, Gianni M. Castiglione, Uri S. Soiberman, Charles G. Eberhart,Elia J. Duha. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. May 9, 2020 preprint on bioRxiv


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