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Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface.
Ocul Surf. 2021 01; 19:190-200.OS

Abstract

PURPOSE

The high infection rate of SARS-CoV-2 necessitates the need for multiple studies identifying the molecular mechanisms that facilitate the viral entry and propagation. Currently the potential extra-respiratory transmission routes of SARS-CoV-2 remain unclear.

METHODS

Using single-cell RNA Seq and ATAC-Seq datasets and immunohistochemical analysis, we investigated SARS-CoV-2 tropism in the embryonic, fetal and adult human ocular surface.

RESULTS

The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2+TMPRSS2+ cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface.

CONCLUSIONS

Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection.

Authors+Show Affiliations

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK; Microscopy Centre and Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, Italy.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.NHS Blood and Transplant Tissue and Eye Services, Liverpool, UK.NHS Blood and Transplant Tissue and Eye Services, Liverpool, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Department of Ophthalmology, Royal Victoria Infirmary and Newcastle University, Newcastle, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK.Biosciences Institute, Faculty of Medical Sciences, Newcastle University, UK. Electronic address: majlinda.lako@ncl.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32502616

Citation

Collin, Joseph, et al. "Co-expression of SARS-CoV-2 Entry Genes in the Superficial Adult Human Conjunctival, Limbal and Corneal Epithelium Suggests an Additional Route of Entry Via the Ocular Surface." The Ocular Surface, vol. 19, 2021, pp. 190-200.
Collin J, Queen R, Zerti D, et al. Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface. Ocul Surf. 2021;19:190-200.
Collin, J., Queen, R., Zerti, D., Dorgau, B., Georgiou, M., Djidrovski, I., Hussain, R., Coxhead, J. M., Joseph, A., Rooney, P., Lisgo, S., Figueiredo, F., Armstrong, L., & Lako, M. (2021). Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface. The Ocular Surface, 19, 190-200. https://doi.org/10.1016/j.jtos.2020.05.013
Collin J, et al. Co-expression of SARS-CoV-2 Entry Genes in the Superficial Adult Human Conjunctival, Limbal and Corneal Epithelium Suggests an Additional Route of Entry Via the Ocular Surface. Ocul Surf. 2021;19:190-200. PubMed PMID: 32502616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface. AU - Collin,Joseph, AU - Queen,Rachel, AU - Zerti,Darin, AU - Dorgau,Birthe, AU - Georgiou,Maria, AU - Djidrovski,Ivo, AU - Hussain,Rafiqul, AU - Coxhead,Jonathan M, AU - Joseph,Agatha, AU - Rooney,Paul, AU - Lisgo,Steven, AU - Figueiredo,Francisco, AU - Armstrong,Lyle, AU - Lako,Majlinda, Y1 - 2020/06/03/ PY - 2020/05/04/received PY - 2020/05/21/revised PY - 2020/05/26/accepted PY - 2020/6/6/pubmed PY - 2021/3/2/medline PY - 2020/6/6/entrez KW - Conjunctiva KW - Cornea KW - ace2 KW - sars-cov-2 KW - tmprss2 SP - 190 EP - 200 JF - The ocular surface JO - Ocul Surf VL - 19 N2 - PURPOSE: The high infection rate of SARS-CoV-2 necessitates the need for multiple studies identifying the molecular mechanisms that facilitate the viral entry and propagation. Currently the potential extra-respiratory transmission routes of SARS-CoV-2 remain unclear. METHODS: Using single-cell RNA Seq and ATAC-Seq datasets and immunohistochemical analysis, we investigated SARS-CoV-2 tropism in the embryonic, fetal and adult human ocular surface. RESULTS: The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2+TMPRSS2+ cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface. CONCLUSIONS: Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection. SN - 1937-5913 UR - https://www.unboundmedicine.com/medline/citation/32502616/Co_expression_of_SARS_CoV_2_entry_genes_in_the_superficial_adult_human_conjunctival_limbal_and_corneal_epithelium_suggests_an_additional_route_of_entry_via_the_ocular_surface_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1542-0124(20)30097-5 DB - PRIME DP - Unbound Medicine ER -