Expression of the COVID-19 receptor ACE2 in the human conjunctiva

J Med Virol. 2020 Oct;92(10):2081-2086. doi: 10.1002/jmv.25981. Epub 2020 Jul 11.

Abstract

SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctivas, 12 melanomas, seven squamous cell carcinomas, and seven papilloma samples, were analyzed using high-throughput RNA sequencing to assess messenger RNA (mRNA) expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median: 0.0 transcripts per million [TPM], min: 0.0 TPM, max: 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; human conjunctiva.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • COVID-19 / complications
  • COVID-19 / pathology
  • COVID-19 / surgery
  • COVID-19 / virology*
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Carcinoma, Squamous Cell / virology*
  • Case-Control Studies
  • Conjunctiva / pathology
  • Conjunctiva / surgery
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Eye Neoplasms / complications
  • Eye Neoplasms / pathology
  • Eye Neoplasms / surgery
  • Eye Neoplasms / virology*
  • Gene Expression
  • Glutamyl Aminopeptidase / genetics
  • Glutamyl Aminopeptidase / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma / complications
  • Melanoma / pathology
  • Melanoma / surgery
  • Melanoma / virology*
  • Middle Aged
  • Papilloma / complications
  • Papilloma / pathology
  • Papilloma / surgery
  • Papilloma / virology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism

Substances

  • RNA, Messenger
  • Receptors, Virus
  • ENPEP protein, human
  • Glutamyl Aminopeptidase
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human