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  1. Article ; Online: SARS-CoV-2 infection in conjunctival tissue.

    Liu, Yu-Chi / Ang, Marcus / Ong, Hon Shing / Wong, Tien Yin / Mehta, Jodhbir S

    The Lancet. Respiratory medicine

    2020  Volume 8, Issue 7, Page(s) e57

    MeSH term(s) Betacoronavirus ; COVID-19 ; Conjunctiva ; Coronavirus Infections ; Humans ; Immunity, Innate ; Pandemics ; Pneumonia, Viral ; Respiratory System ; SARS-CoV-2 ; Tropism
    Keywords covid19
    Language English
    Publishing date 2020-07-09
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/S2213-2600(20)30272-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SARS-CoV-2 infection in conjunctival tissue - Authors' reply.

    Hui, Kenrie Py / Peiris, Malik / Nicholls, J M / Chan, Michael Cw

    The Lancet. Respiratory medicine

    2020  Volume 8, Issue 7, Page(s) e58

    MeSH term(s) Betacoronavirus ; COVID-19 ; Conjunctiva ; Coronavirus Infections ; Humans ; Immunity, Innate ; Pandemics ; Pneumonia, Viral ; Respiratory System ; SARS-CoV-2 ; Tropism
    Keywords covid19
    Language English
    Publishing date 2020-07-09
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/S2213-2600(20)30273-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: SARS-CoV-2 infection in conjunctival tissue

    Liu, Yu-Chi / Ang, Marcus / Ong, Hon Shing / Wong, Tien Yin / Mehta, Jodhbir S

    The Lancet Respiratory Medicine

    2020  Volume 8, Issue 7, Page(s) e57

    Keywords Pulmonary and Respiratory Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/s2213-2600(20)30272-1
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: SARS-CoV-2 infection in conjunctival tissue – Authors' reply

    Hui, Kenrie PY / Peiris, Malik / Nicholls, JM / Chan, Michael CW

    The Lancet Respiratory Medicine

    2020  Volume 8, Issue 7, Page(s) e58

    Keywords Pulmonary and Respiratory Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/s2213-2600(20)30273-3
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Effects of particulate matter exposure on the expression of the SARS-CoV-2 ACE2 receptor in ocular surface tissues and cells.

    Li, Xiangzhe / Li, Xuemin / Kang, Boram / Eom, Youngsub / Lee, Hyung Keun / Kim, Dong Hyun / Zhong, Jingxiang / Song, Jong Suk

    Environmental science and pollution research international

    2024  Volume 31, Issue 6, Page(s) 8768–8780

    Abstract: ... term PM exposure down-regulate the expression of the SARS-CoV-2 receptor ACE2 in conjunctival tissues ... exposure and SARS-COV-2 infection, no studies have investigated the effects of PM exposure on the ocular ... route of SARS-COV-2 infection. To this end, we explored the effects of PM on the expression of SARS-COV ...

    Abstract Particulate matter (PM) has been reported to be one of the risk factor for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, although the ocular surface is deeply affected by both PM exposure and SARS-COV-2 infection, no studies have investigated the effects of PM exposure on the ocular route of SARS-COV-2 infection. To this end, we explored the effects of PM on the expression of SARS-COV-2-associated receptors and proteins in ocular surface. Herein, short- and long-term PM-exposed rat models were established by topically administering PM for 3 and 10 days, respectively. Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to PM. ACE2, TMPRSS2, CD147, and ADAM17 expression levels were measured by western blot analysis. Our results show that short-term PM exposure had little effect on the expressions of ACE2, TMPRSS2, and CD147 in ocular surface tissues. However, long-term PM exposure decreased the ACE2 expression in conjunctival tissues and increased the CD147 expression in corneal or conjunctival tissues. PM exposure reduced the ACE2 expression by increasing the ADAM17 expression and ACE2 shedding level in HCECs and HCjECs. Our findings suggest that long-term PM exposure down-regulate the expression of the SARS-CoV-2 receptor ACE2 in conjunctival tissues through ADAM17-dependent ACE2 shedding. However, long-term PM exposure up-regulates the expression of another SARS-CoV-2 receptor CD147 in ocular surface tissues, accompanied by ocular surface damage and cytotoxicity. This study provides a new insight into uncovering potential risk factors for infection with SARS-CoV-2 via the ocular route.
    MeSH term(s) Humans ; Rats ; Animals ; SARS-CoV-2 ; COVID-19/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Particulate Matter/metabolism ; Conjunctiva/metabolism
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Particulate Matter
    Language English
    Publishing date 2024-01-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1178791-0
    ISSN 1614-7499 ; 0944-1344
    ISSN (online) 1614-7499
    ISSN 0944-1344
    DOI 10.1007/s11356-023-31607-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Expression of the SARS-CoV-2 Receptor ACE2 and Protease TMPRSS2 in Ocular Hypertension Eyes of Nonhuman Primate and Human.

    Sun, Difang / Zhan, Zongyi / Wang, Bin / Liu, Ting / Yu, Minbin / Lan, Yuqing / Li, Jun

    Current eye research

    2024  Volume 49, Issue 3, Page(s) 270–279

    Abstract: ... to severe acute respiratory syndrome coronavirus 2 infection. ... severe acute respiratory syndrome coronavirus 2. The double-positive of angiotensin-converting enzyme 2 and transmembrane ... protease serine type 2 have a higher risk of being infected by severe acute respiratory syndrome coronavirus 2 ...

    Abstract Purpose: Coronavirus disease 2019 is a disease caused by the novel severe acute respiratory syndrome coronavirus 2. The double-positive of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 have a higher risk of being infected by severe acute respiratory syndrome coronavirus 2. The susceptibility of coronavirus disease 2019 in patients with chronic diseases, especially in different tissues of ocular hypertension eyes like glaucoma, is not yet known.
    Methods: An ocular hypertension model was established by laser photocoagulation in rhesus monkeys. The expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in three ocular hypertension eyes and the three control eyes were analyzed using immunofluorescence.
    Results: No difference was observed between ocular hypertension and control eyes in the expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in the conjunctival epithelium, corneal epithelium, and ciliary muscle. In ocular hypertension eyes and control eyes, angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression were both observed in the retina. Angiotensin-converting enzyme 2 staining of retinal ganglion cells was found to be significantly higher in ocular hypertension eyes than in control eyes. However, there was no difference in angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression in retinal vessels and choroidal vessels between ocular hypertension and control eyes. In our study, the expression and distribution of angiotensin-converting enzyme 2 and TMPREE2 in human retina were similar to that of non-human primates as expected.
    Conclusion: Our study confirmed that angiotensin-converting enzyme 2 and transmembrane protease serine type 2 were expressed widely in rhesus monkey eyes. When compared with controls eyes, the expression of angiotensin-converting enzyme 2 was higher in the retinal ganglion cells in ocular hypertension eyes, suggesting that high ocular pressure may affect the patients' ocular susceptibility to severe acute respiratory syndrome coronavirus 2 infection.
    MeSH term(s) Animals ; Humans ; SARS-CoV-2 ; COVID-19 ; Angiotensin-Converting Enzyme 2/metabolism ; Peptide Hydrolases ; Peptidyl-Dipeptidase A/metabolism ; Ocular Hypertension ; Glaucoma ; Serine ; Serine Endopeptidases
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Peptide Hydrolases (EC 3.4.-) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Serine (452VLY9402) ; TMPRSS2 protein, human (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-)
    Language English
    Publishing date 2024-01-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 82079-9
    ISSN 1460-2202 ; 0271-3683
    ISSN (online) 1460-2202
    ISSN 0271-3683
    DOI 10.1080/02713683.2023.2291749
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Conjunctival epithelial cells resist productive SARS-CoV-2 infection.

    Jackson, Robert M / Hatton, Catherine F / Spegarova, Jarmila Stremenova / Georgiou, Maria / Collin, Joseph / Stephenson, Emily / Verdon, Bernard / Haq, Iram J / Hussain, Rafiqul / Coxhead, Jonathan M / Mudhar, Hardeep-Singh / Wagner, Bart / Hasoon, Megan / Davey, Tracey / Rooney, Paul / Khan, C M Anjam / Ward, Chris / Brodlie, Malcolm / Haniffa, Muzlifah /
    Hambleton, Sophie / Armstrong, Lyle / Figueiredo, Francisco / Queen, Rachel / Duncan, Christopher J A / Lako, Majlinda

    Stem cell reports

    2022  Volume 17, Issue 7, Page(s) 1699–1713

    Abstract: ... innate immune response to SARS-CoV-2 infection in conjunctival cells was characterised by a robust autocrine and ... to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome expression, a productive infection did not ensue. The early ... enrich our understanding of SARS-CoV-2 infection at the human ocular surface, with potential implications ...

    Abstract Conjunctival epithelial cells, which express viral-entry receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2), constitute the largest exposed epithelium of the ocular surface tissue and may represent a relevant viral-entry route. To address this question, we generated an organotypic air-liquid-interface model of conjunctival epithelium, composed of basal, suprabasal, and superficial epithelial cells, and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single-cell RNA sequencing (RNA-seq), with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome expression, a productive infection did not ensue. The early innate immune response to SARS-CoV-2 infection in conjunctival cells was characterised by a robust autocrine and paracrine NF-κB activity, without activation of antiviral interferon signalling. Collectively, these data enrich our understanding of SARS-CoV-2 infection at the human ocular surface, with potential implications for the design of preventive strategies and conjunctival transplantation.
    MeSH term(s) COVID-19 ; Epithelial Cells/metabolism ; Humans ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Receptors, Virus/metabolism ; SARS-CoV-2
    Chemical Substances Receptors, Virus ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language English
    Publishing date 2022-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2720528-9
    ISSN 2213-6711 ; 2213-6711
    ISSN (online) 2213-6711
    ISSN 2213-6711
    DOI 10.1016/j.stemcr.2022.05.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

    Monu, Monu / Ahmad, Faraz / Olson, Rachel M / Balendiran, Vaishnavi / Singh, Pawan Kumar

    PLoS pathogens

    2024  Volume 20, Issue 4, Page(s) e1012156

    Abstract: ... The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund ... Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection ... SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID ...

    Abstract SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina. Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.
    MeSH term(s) SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Animals ; Blood-Retinal Barrier/virology ; COVID-19/immunology ; COVID-19/virology ; Mice ; Humans ; Retina/virology ; Retina/immunology ; Retina/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Virus Internalization ; Spike Glycoprotein, Coronavirus/metabolism ; Spike Glycoprotein, Coronavirus/immunology ; Inflammation/immunology ; Inflammation/virology ; Betacoronavirus/physiology ; Viral Tropism ; Coronavirus Infections/immunology ; Coronavirus Infections/virology ; Coronavirus Infections/pathology
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Ace2 protein, mouse (EC 3.4.17.23)
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1012156
    Database MEDical Literature Analysis and Retrieval System OnLINE

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