{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:52:07Z","timestamp":1768488727308,"version":"3.49.0"},"posted":{"date-parts":[[2020,5,9]]},"group-title":"Pathology","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T00:00:00Z","timestamp":1588982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,5,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Conjunctival 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Across 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together, 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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.05.09.086165","type":"posted-content","created":{"date-parts":[[2020,5,10]],"date-time":"2020-05-10T06:29:33Z","timestamp":1589092173000},"source":"Crossref","is-referenced-by-count":26,"title":["ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9321-9348","authenticated-orcid":false,"given":"Lingli","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0768-4236","authenticated-orcid":false,"given":"Gianni M.","family":"Castiglione","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uri S.","family":"Soiberman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles G.","family":"Eberhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elia J.","family":"Duh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080404232498000_2020.05.09.086165v1.1","doi-asserted-by":"crossref","unstructured":"Wu P , Duan F , Luo C , Liu Q , Qu X , Liang L , et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA ophthalmology. 2020.","DOI":"10.1001\/jamaophthalmol.2020.1291"},{"key":"2024080404232498000_2020.05.09.086165v1.2","doi-asserted-by":"crossref","unstructured":"Seah IYJ , Anderson DE , Kang AEZ , Wang L , Rao P , Young BE , et al. Assessing Viral Shedding and Infectivity of Tears in Coronavirus Disease 2019 (COVID-19) Patients. Ophthalmology. 2020.","DOI":"10.1016\/j.ophtha.2020.03.026"},{"key":"2024080404232498000_2020.05.09.086165v1.3","doi-asserted-by":"crossref","unstructured":"Zhang X , Chen X , Chen L , Deng C , Zou X , Liu W , et al. The evidence of SARS-CoV-2 infection on ocular surface. Ocul Surf. 2020.","DOI":"10.1016\/j.jtos.2020.03.010"},{"key":"2024080404232498000_2020.05.09.086165v1.4","doi-asserted-by":"crossref","unstructured":"Jun ISY , Hui KKO , Songbo PZ . Perspectives on Coronavirus Disease 2019 Control Measures for Ophthalmology Clinics Based on a Singapore Center Experience. JAMA ophthalmology. 2020.","DOI":"10.1001\/jamaophthalmol.2020.1288"},{"key":"2024080404232498000_2020.05.09.086165v1.5","doi-asserted-by":"crossref","unstructured":"Napoli PE , Nioi M , d\u2019Aloja E , Fossarello M. The Ocular Surface and the Coronavirus Disease 2019: Does a Dual \u2018Ocular Route\u2019 Exist? J Clin Med. 2020;9.","DOI":"10.3390\/jcm9051269"},{"key":"2024080404232498000_2020.05.09.086165v1.6","doi-asserted-by":"crossref","unstructured":"Sungnak W , Huang N , Becavin C , Berg M , Queen R , Litvinukova M , et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. 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Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. The Lancet Respiratory Medicine. 2020.","DOI":"10.1016\/S2213-2600(20)30193-4"},{"key":"2024080404232498000_2020.05.09.086165v1.24","doi-asserted-by":"crossref","unstructured":"Lange C , Wolf J , Auw-Haedrich C , Schlecht A , Boneva S , Lapp T , et al. Expression of the COVID-19 receptor ACE2 in the human conjunctiva. 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