ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection

Abstract

PurposeConjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection.MethodsWe analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2.ResultsAcross all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.ConclusionsTogether, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.

SARS-CoV-2 Infectivity and Neurological Targets in the Brain

“…With regard to pathogenicity, spike (S) proteins are essential for viral entry into host cells (Du et al 2017;Guan et al 2020;Li et al 2020a, b;Zubair et al 2019). SARS-CoV-2 appears to bind exclusively to the angiotensin-converting enzyme (ACE2) protein, a single-pass type 1 transmembrane receptor with its enzymatically active domain exposed on the surface of multiple cell types, such as type II alveolar cells of the respiratory system, enterocytes and intestinal epithelial cells, endothelial cells, epithelial cells of the conjunctival epithelium, kidney cells (renal tubules) and certain immune cells, such as alveolar monocytes/macrophages and certain cells of the CNS including those of the cerebral cortex and brainstem (Guan et al 2020;Kabbani et al 2020;Li et al 2020a, b;Zhou et al 2020;Zubair et al 2019). More specifically, the binding of the spike S1 protein of both SARS-CoV and SARS-CoV-2 to the enzymatic domain of ACE2 on the surface of cells results in the endocytosis and translocation of both SARS-CoV-2 and the ACE2 enzyme into endosomes of infected cells (Wang et al 2008;Millet and Whittaker 2018;Lewis 2020).…”

“…More specifically, the binding of the spike S1 protein of both SARS-CoV and SARS-CoV-2 to the enzymatic domain of ACE2 on the surface of cells results in the endocytosis and translocation of both SARS-CoV-2 and the ACE2 enzyme into endosomes of infected cells (Wang et al 2008;Millet and Whittaker 2018;Lewis 2020). The cell surface associated transmembrane serine protease 2 TMPRSS2 (epitheliasin; EC 3.4.21.109) also facilitates CoV-19 entry into cells following binding of the viral spike protein S1 to ACE2 (https ://www.genec ards.org/cgi-bin/cardd isp.pl?gene=TMPRS S2; Zhou et al 2020). The inhibition of SARS-CoV-2 and ACE2 recognition, TMPRSS2 signaling and SARS-CoV-2 translocation into host cells is currently under extremely intense research investigation as a cornerstone to the implementation of prospective and efficacious anti-SARS-CoV-2 therapeutic strategies (Akhmerov and Marbán 2020;Bourgonje et al 2020;Datta et al 2020;Saavedra 2020;Shang et al 2020).…”

SARS-CoV-2: Impact on, Risk Assessment and Countermeasures in German Eye Banks

“…[19][20][21][22] However, recent studies demonstrated the presence of both ACE-Receptor and TMPRSS2 serine protease in corneal and in lower concentrations also in conjunctiva. 23,24 Furthermore, SARS-CoV-2 first attaches to cells via heparan sulfate proteoglycans before binding ACE2, but lactoferrin, present in high concentration (2 mg/ml) in tears, can inhibit the binding of SARS-CoV to its attachment receptor. 6 Even under the supposition that SARS-CoV-2 could adhere to the human ACE receptors present in corneal epithelium, the question remains if it could survive corneal transplant procurement and storage.…”

Effect of COVID-19 on the Organs

“…Both ACE2 receptors and TMPRSS2 proteases that are necessary for infection by SARS-CoV-2 are found in ocular surface cells in cornea, inside the eyelids and in the white of the eye [43]. About one-third of hospitalized patients develop ocular abnormalities including conjunctivitis [44].…”