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Characterization of SARS-CoV-2 Entry Factors' Expression in Corneal and Limbal Tissues of Adult Human Donors Aged from 58 to 85.
J Ocul Pharmacol Ther. 2022 Jan-Feb; 38(1):56-65.JO

Abstract

Purpose: Recent studies have shown the presence of SARS-CoV-2 entry factors on the ocular surface, identifying the eye as an additional entry route for the virus. Moreover, the coexpression of angiotensin-converting enzyme 2 (ACE2) with other SARS-CoV-2 entry factors [transmembrane protease serine 2 (TMPRSS2), transmembrane protease serine 4 (TMPRSS4), and dipeptidyl peptidase-4 (DPP4)] facilitates the virus infection. Methods: Here, we performed a study over 10 adult corneal and limbal tissues from human donors, both male and female between 58 and 85 years of age. Some of the main virus entry factors were analyzed and their expression was quantified and correlated with the age and sex of the donors through western blot. The receptors' localization was investigated through immunofluorescence. Results: Immunofluorescence confirmed the localization of ACE2 and TMPRSS2 on the ocular surface and showed, for the first time, the localization of TMPRSS4 and DPP4 in limbal and corneal epithelial superficial cells. The quantitative analysis showed that the expression of SARS-CoV-2 entry factors on corneal and limbal cells is likely to be modulated in an age-dependent manner, in agreement with the increased susceptibility to COVID-19 in the elderly. Moreover, we found a relationship between the expression of TMPRSS proteases with the activation state of limbal cells in 80-year-old donors. Conclusion: This study provides information on the expression of SARS-CoV-2 entry factors on the ocular surface of 10 adult human donors and is a first observation of a possible age-dependent modulation on corneal and limbal tissues. Our data pave the way to further investigate the susceptibility to the infection through the ocular surface in the elderly.

Authors+Show Affiliations

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.UOSD Eye Bank of L'Aquila - C.R.R. for corneas donation and transplantation for Abruzzo and Molise regions, S. Salvatore Hospital, L'Aquila, Italy.UOSD Eye Bank of L'Aquila - C.R.R. for corneas donation and transplantation for Abruzzo and Molise regions, S. Salvatore Hospital, L'Aquila, Italy.UOSD Eye Bank of L'Aquila - C.R.R. for corneas donation and transplantation for Abruzzo and Molise regions, S. Salvatore Hospital, L'Aquila, Italy.Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34889660

Citation

Tisi, Annamaria, et al. "Characterization of SARS-CoV-2 Entry Factors' Expression in Corneal and Limbal Tissues of Adult Human Donors Aged From 58 to 85." Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics, vol. 38, no. 1, 2022, pp. 56-65.
Tisi A, Zerti D, Genitti G, et al. Characterization of SARS-CoV-2 Entry Factors' Expression in Corneal and Limbal Tissues of Adult Human Donors Aged from 58 to 85. J Ocul Pharmacol Ther. 2022;38(1):56-65.
Tisi, A., Zerti, D., Genitti, G., Vicentini, M. T., Baccante, M., Flati, V., & Maccarone, R. (2022). Characterization of SARS-CoV-2 Entry Factors' Expression in Corneal and Limbal Tissues of Adult Human Donors Aged from 58 to 85. Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics, 38(1), 56-65. https://doi.org/10.1089/jop.2021.0085
Tisi A, et al. Characterization of SARS-CoV-2 Entry Factors' Expression in Corneal and Limbal Tissues of Adult Human Donors Aged From 58 to 85. J Ocul Pharmacol Ther. 2022 Jan-Feb;38(1):56-65. PubMed PMID: 34889660.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of SARS-CoV-2 Entry Factors' Expression in Corneal and Limbal Tissues of Adult Human Donors Aged from 58 to 85. AU - Tisi,Annamaria, AU - Zerti,Darin, AU - Genitti,Germano, AU - Vicentini,Maria Teresa, AU - Baccante,Mariangela, AU - Flati,Vincenzo, AU - Maccarone,Rita, Y1 - 2021/12/07/ PY - 2021/12/11/pubmed PY - 2022/2/10/medline PY - 2021/12/10/entrez KW - COVID-19 KW - SARS-CoV-2 KW - cornea KW - limbus KW - ocular surface SP - 56 EP - 65 JF - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics JO - J Ocul Pharmacol Ther VL - 38 IS - 1 N2 - Purpose: Recent studies have shown the presence of SARS-CoV-2 entry factors on the ocular surface, identifying the eye as an additional entry route for the virus. Moreover, the coexpression of angiotensin-converting enzyme 2 (ACE2) with other SARS-CoV-2 entry factors [transmembrane protease serine 2 (TMPRSS2), transmembrane protease serine 4 (TMPRSS4), and dipeptidyl peptidase-4 (DPP4)] facilitates the virus infection. Methods: Here, we performed a study over 10 adult corneal and limbal tissues from human donors, both male and female between 58 and 85 years of age. Some of the main virus entry factors were analyzed and their expression was quantified and correlated with the age and sex of the donors through western blot. The receptors' localization was investigated through immunofluorescence. Results: Immunofluorescence confirmed the localization of ACE2 and TMPRSS2 on the ocular surface and showed, for the first time, the localization of TMPRSS4 and DPP4 in limbal and corneal epithelial superficial cells. The quantitative analysis showed that the expression of SARS-CoV-2 entry factors on corneal and limbal cells is likely to be modulated in an age-dependent manner, in agreement with the increased susceptibility to COVID-19 in the elderly. Moreover, we found a relationship between the expression of TMPRSS proteases with the activation state of limbal cells in 80-year-old donors. Conclusion: This study provides information on the expression of SARS-CoV-2 entry factors on the ocular surface of 10 adult human donors and is a first observation of a possible age-dependent modulation on corneal and limbal tissues. Our data pave the way to further investigate the susceptibility to the infection through the ocular surface in the elderly. SN - 1557-7732 UR - https://www.unboundmedicine.com/medline/citation/34889660/Characterization_of_SARS_CoV_2_Entry_Factors'_Expression_in_Corneal_and_Limbal_Tissues_of_Adult_Human_Donors_Aged_from_58_to_85_ DB - PRIME DP - Unbound Medicine ER -