Comparative transcriptome analysis of human conjunctiva between normal and conjunctivochalasis persons by RNA sequencing

Xiang, Minhong; Zhang, Wei; Huang, Wen; Mo, Lijuan; Zhao, Yanqing; Zhan, Yueping

doi:10.1016/j.exer.2019.04.005

Cited by 16 publications

(15 citation statements)

References 31 publications

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“…This study shows that ACE2 , which is the main receptor for SARS‐CoV‐2, 6 is not significantly expressed in healthy and diseased human conjunctival samples. The results of this study are consistent with previously published transcriptomic datasets showing a very low expression of ACE2 in conjunctival samples 22 . In line with the low ACE2 mRNA levels, we found a negligible ACE2 immunoreactivity, indicating insignificant ACE2 protein expression in the conjunctiva.…”

Section: Discussionsupporting

confidence: 93%

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

Lange

Wolf

Auw-Haedrich

et al. 2020

Journal of Medical Virology

121

108

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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 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 conjunctiva, 12 melanoma, 7 squamous cell carcinoma and 7 papilloma samples, were analyzed using high-throughput RNA sequencing to assess mRNA expression of the SARS-CoV-2 receptor ACE2 and its cofactors including This article is protected by copyright. All rights reserved. Accepted ArticleTMPRSS2, 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.

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Section: Discussionsupporting

confidence: 93%

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

Lange

Wolf

Auw-Haedrich

et al. 2020

Journal of Medical Virology

121

108

View full text Add to dashboard Cite

show abstract

“…The mean level of ACE2 or TMPRSS2 mRNA expression in each ocular tissue was around 0.6%, whereas the mean level of expression in most other tissues investigated (such as nasal cavity, lung parenchyma, ileum, colon, heart) was higher, at 1.2-1.4% [23]. The results of these two studies are in line with a previously published transcriptome analysis showing very low expression of ACE2 in conjunctival samples [24].…”

Section: Expression In Corneal and Conjunctival Epithelial Cellssupporting

confidence: 89%

Can SARS-CoV-2 infect the eye? An overview of the receptor status in ocular tissue

et al. 2020

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Is the new coronavirus SARS-CoV‑2 able to infect ocular tissue and thus poses a risk of infection through the tissue in addition to the risk of contact? This is the question that has occupied ophthalmologists since the beginning of the outbreak. In order to infect a certain type of tissue specific receptors for each virus and sometimes also coreceptors or other proteins must be present. The aim of this review was to summarize and reflect the current state of research with the help of the currently available literature as of 28 May 2020. At the time of the research, angiotensin-converting enzyme 2 (ACE2) was clearly identified as the receptor and transmembrane serine protease 2 (TMPRSS2) as the necessary protease to enable the infection of human cells with SARS-CoV‑2. In the eye both ACE2 and TMPRSS2 are expressed, although sometimes very weakly and with varying degrees in different tissues. It is noteworthy that very different results were obtained with different methods. Several reasons can account for this effect: Firstly, the method of detection or preservation of the tissue, secondly, the possibly different expression of the tested tissue samples and thirdly, a possibly rapid loss of receptor expression post-mortem. Therefore, an infection of the eye seems possible, which has already been reported in various publications. The amount of virus or receptor expression necessary to cause an infection is not known. According to current state of knowledge the eye is not considered to be a high-risk tissue due to the low ACE2 and TMPRSS2 expression. Nevertheless, appropriate protective measures are necessary for both medical personnel and patients. In cases of corneal transplantation an infection of the donor tissue with SARS-CoV‑2 must be excluded.

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“…Additionally, our previous transcriptome analysis of CCH conjunctival tissues and normal conjunctival tissues showed that the dysregulated genes (fold change ‡ 2, q value < 0.05) between CCH conjunctival tissues and normal conjunctival tissues significantly were enriched in the p53 signaling pathway. 28 The dysregulated genes PLA2R1 and TERT, enriched in cellular senescence-associated GO terms, were markedly downregulated in CCH conjunctival tissues. All these results indicated the important role of cellular senescence in CCH.…”

Section: Discussionmentioning

confidence: 94%

“…A total of 757 genes that dysregulated in CCH conjunctival tissues compared with normal conjunctival tissues were identified by our previous study. 28 The overlapping genes among all genes involved in cellular senescence-associated GO terms and 757 differentially expressed genes (DEGs) were identified as cellular senescence-associated genes that associated with CCH.…”

Section: Identification Of Cellular Senescence-associated Genesmentioning

confidence: 99%

P38-Mediated Cellular Senescence in Conjunctivochalasis Fibroblasts

Xiang

Zhan

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Conjunctivochalasis (CCH) is a common ocular disease and has received extensive attention recently. However, its exact pathogenesis remains largely unknown. Owing to the high morbidity of CCH in older people, this study aimed to investigate whether cellular senescence contributes to CCH progression and the underlying mechanism. METHODS. Loose conjunctival tissues from CCH patients (n ¼ 13) and normal conjunctival tissues from age-matched persons (n ¼ 12) were obtained and the fibroblasts were separately induced and obtained. Cellular senescence, and the expression of senescence-associated genes (p53 and p21) and p38 in CCH conjunctival tissues and normal controls, were determined by senescence-associated b-galactosidase (SA-b-Gal) staining and quantitative (q)RT-PCR, respectively. To explore the effects of p38 on cellular senescence in CCH fibroblasts, small interfering RNA (siRNA) targeting p38 (siP38) and p38-specific inhibitor SB203580 was performed in CCH fibroblasts. Then, cellular senescence, cell viability, reactive oxygen species (ROS) production, and gene expression were detected according to the corresponding methods. RESULTS. CCH conjunctival tissues had significantly more senescent cells, evidenced by more SA-b-Gal-positive cells, and higher expression of senescence-associated genes (p53 and p21) and p38. CCH fibroblasts transfected with siP38 or treated with SB203580 had obviously reduced numbers of senescent cells, decreased ROS production, and increased cell viability, as well as reduced expression of senescence-associated genes. Meanwhile, blocking p38 signaling decreased the expression of p53 and p21. CONCLUSIONS. Therefore, these findings indicate that cellular senescence might be a causative factor for CCH. P38 signaling might play an important role in the progress of cellular senescence in CCH fibroblasts via manipulation of p53/p21 signaling.

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Comparative transcriptome analysis of human conjunctiva between normal and conjunctivochalasis persons by RNA sequencing

Cited by 16 publications

References 31 publications

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

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

Can SARS-CoV-2 infect the eye? An overview of the receptor status in ocular tissue

P38-Mediated Cellular Senescence in Conjunctivochalasis Fibroblasts

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