Related Experiment Video
Updated: Oct 4, 2025
Author Spotlight: Anterior HR-OCT as a Non-Invasive Tool for Characterizing Ocular Surface Squamous Neoplasia
Published on: August 9, 2024
Tracing the SARS-CoV-2 infection on the ocular surface: Overview and preliminary corneoscleral transcriptome
Umberto Rosani1, Claudia Del Vecchio2, Elisa Franchin2
1Department of Biology, University of Padova, Italy.
Abstract:
COVID-19's impact on the ocular surface has already been recognized, however the molecular mechanisms induced by the infection on the ocular surface are still unclear. The aim of this paper is to provide a first overview of the transcriptional perturbations caused by SARS-CoV-2 on the ocular surface by analyzing gene expression profile of corneoscleral ring samples from post-mortem SARS-CoV-2 positive donors (PD). The presence of SARS-CoV-2 on the ocular surface, in tears and corneal tissues has rarely been detected in infected individuals in both the presence and the absence of ocular manifestations. In this preliminary study, 6 human corneoscleral tissues of 3 PD and two tissues from a negative donor (CTRL) were obtained at the local eye bank. The presence of genomic and sub-genomic SARS-CoV-2 RNAs was assessed by qRT-PCR, while transcriptome analysis (RNA-sequencing) was performed by Illumina. Principal Component Analysis (PCA), search for differentially expressed genes (DEGs) and Gene Ontology (GO)-enrichment analysis were performed. Three samples from PD were found positive for SARS-CoV-2 genomic RNA, although the absence of sub-genomic RNAs indicated an inactive virus. PCA analysis grouped 3 different clusters, one including CTRL, and the other two including, respectively, PD with undetected SARS-CoV-2 (PD-SARS-neg) and PD with detected SARS-CoV-2 (PD-SARS-pos). The DEGs in common with the 2 PD clusters included several genes associable to the interferon pathway, such as ADAMTS4, RSAD2, MMP1, IL6, ISG15 and proinflammatory cytokines. Among the down-regulated genes we found AQP5. GO analysis revealed 77 GO terms over-represented in PD-SARS-neg vs. CTRL, and 17 GO terms in PD-SARS-pos vs. CTRL. The presence of SARS-CoV-2 RNA and RNA-sequencing reads in ocular surface tissues supports the possibility that the eye acts as an entry route. The modulation of early responsive genes, together with several ISGs suggests a potential protective responsiveness of the ocular tissues to SARS-CoV-2.
Insights
This study reveals SARS-CoV-2 RNA in post-mortem eye tissues, showing interferon pathway activation and potential protective responses in ocular tissues. The findings offer insights into the molecular mechanisms of COVID-19 on the ocular surface.
Area of Science:
- Ophthalmology
- Virology
- Molecular Biology
- Immunology
Background:
- The ocular surface's response to SARS-CoV-2 infection is not fully understood at the molecular level.
- Previous research has rarely detected SARS-CoV-2 in ocular tissues, leaving mechanisms unclear.
- Understanding the ocular surface's transcriptional changes during COVID-19 is crucial for managing potential complications.
Purpose of the Study:
- To investigate the transcriptional perturbations induced by SARS-CoV-2 on the human ocular surface.
- To analyze gene expression profiles in corneoscleral ring samples from post-mortem SARS-CoV-2 positive donors.
- To explore the potential role of the eye as an entry route and its immune response to SARS-CoV-2.
Main Methods:
- Analysis of corneoscleral ring tissues from post-mortem SARS-CoV-2 positive (PD) and negative (CTRL) donors.
- Detection of SARS-CoV-2 genomic and sub-genomic RNA using quantitative reverse transcription PCR (qRT-PCR).
- Transcriptome analysis via RNA-sequencing, followed by Principal Component Analysis (PCA), differential gene expression (DEG) analysis, and Gene Ontology (GO) enrichment analysis.
Main Results:
- SARS-CoV-2 genomic RNA was detected in three PD samples, suggesting inactive viral presence.
- PCA analysis revealed distinct clusters for CTRL, PD-SARS-neg, and PD-SARS-pos samples.
- Differentially expressed genes common to both PD groups were associated with the interferon pathway and inflammation (e.g., ADAMTS4, RSAD2, MMP1, IL6, ISG15), with AQP5 being downregulated.
Conclusions:
- The presence of SARS-CoV-2 RNA in ocular tissues supports the eye's potential as an entry route for the virus.
- Gene expression analysis indicates modulation of early responsive genes and interferon-stimulated genes (ISGs) in ocular tissues.
- These findings suggest a potential protective immune responsiveness of ocular tissues to SARS-CoV-2 infection.
