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Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface.
Cornea. 2020 Dec; 39(12):1556-1562.C

Abstract

PURPOSE

To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry.

METHODS

Fresh donor corneas and primary explant cultures of corneal, limbal, and conjunctival epithelial cells were evaluated for the expression of viral entry factors. Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2).

RESULTS

In total, 5 donor corneas were evaluated for the expression of viral entry factors. In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. DC-SIGN/DC-SIGNR expression varied between donor specimens. Four specimens expressed DC-SIGN/DC-SIGNR in a similar distribution to ACE2, but 1 specimen from a young donor showed no expression of DC-SIGN/DC-SIGNR. ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells.

CONCLUSIONS

Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2. The risk of viral transmission with corneal transplantation cannot be ruled out, given the presence of ACE2 in corneal epithelium and endothelium. Cultured corneal, limbal, and conjunctival epithelial cells mimic the expression of viral entry factors in fresh donor tissue and may be useful for future in vitro SARS-CoV-2 infection studies.

Authors+Show Affiliations

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN; and.Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN; and. Lions Gift of Sight Eye Bank, St. Paul, MN.Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN; and. Lions Gift of Sight Eye Bank, St. Paul, MN.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32826650

Citation

Roehrich, Heidi, et al. "Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface." Cornea, vol. 39, no. 12, 2020, pp. 1556-1562.
Roehrich H, Yuan C, Hou JH. Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface. Cornea. 2020;39(12):1556-1562.
Roehrich, H., Yuan, C., & Hou, J. H. (2020). Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface. Cornea, 39(12), 1556-1562. https://doi.org/10.1097/ICO.0000000000002509
Roehrich H, Yuan C, Hou JH. Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface. Cornea. 2020;39(12):1556-1562. PubMed PMID: 32826650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface. AU - Roehrich,Heidi, AU - Yuan,Ching, AU - Hou,Joshua H, PY - 2020/8/23/pubmed PY - 2020/11/21/medline PY - 2020/8/23/entrez SP - 1556 EP - 1562 JF - Cornea JO - Cornea VL - 39 IS - 12 N2 - PURPOSE: To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry. METHODS: Fresh donor corneas and primary explant cultures of corneal, limbal, and conjunctival epithelial cells were evaluated for the expression of viral entry factors. Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2). RESULTS: In total, 5 donor corneas were evaluated for the expression of viral entry factors. In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. DC-SIGN/DC-SIGNR expression varied between donor specimens. Four specimens expressed DC-SIGN/DC-SIGNR in a similar distribution to ACE2, but 1 specimen from a young donor showed no expression of DC-SIGN/DC-SIGNR. ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells. CONCLUSIONS: Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2. The risk of viral transmission with corneal transplantation cannot be ruled out, given the presence of ACE2 in corneal epithelium and endothelium. Cultured corneal, limbal, and conjunctival epithelial cells mimic the expression of viral entry factors in fresh donor tissue and may be useful for future in vitro SARS-CoV-2 infection studies. SN - 1536-4798 UR - https://www.unboundmedicine.com/medline/citation/32826650/Immunohistochemical_Study_of_SARS_CoV_2_Viral_Entry_Factors_in_the_Cornea_and_Ocular_Surface_ DB - PRIME DP - Unbound Medicine ER -