Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus.
WGS
cornea
corneal epithelium
inflammation
keratoconus
non-coding sequence variation
whole genome
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
30
03
2023
accepted:
09
06
2023
medline:
25
7
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
epublish
Résumé
Keratoconus (KTCN) is the most common corneal ectasia resulting in a conical shape of the cornea. Here, genomic variation in the corneal epithelium (CE) across the keratoconic cone surface in patients with KTCN and its relevance in the functioning of the immune system were assessed. Samples from four unrelated adolescent patients with KTCN and two control individuals were obtained during the CXL and PRK procedures, respectively. Three First, pathway enrichment analysis of genes with identified coding variants pointed to "Antigen presentation" and "Interferon alpha/beta signaling" as the most overrepresented pathways, indicating the involvement of inflammatory responses in KTCN. Both coding and non-coding sequence variants were found in genes (or in their close proximity) linked to the previously revealed KTCN-specific cellular components, namely, "Actin cytoskeleton", "Extracellular matrix", "Collagen-containing extracellular matrix", "Focal adhesion", "Hippo signaling pathway", and "Wnt signaling" pathways. No genomic heterogeneity across the corneal surface was found comparing the assessed The identified genomic features indicate the involvement of innate and adaptive immune system responses in KTCN pathogenesis.
Sections du résumé
Background
Keratoconus (KTCN) is the most common corneal ectasia resulting in a conical shape of the cornea. Here, genomic variation in the corneal epithelium (CE) across the keratoconic cone surface in patients with KTCN and its relevance in the functioning of the immune system were assessed.
Methods
Samples from four unrelated adolescent patients with KTCN and two control individuals were obtained during the CXL and PRK procedures, respectively. Three
Results
First, pathway enrichment analysis of genes with identified coding variants pointed to "Antigen presentation" and "Interferon alpha/beta signaling" as the most overrepresented pathways, indicating the involvement of inflammatory responses in KTCN. Both coding and non-coding sequence variants were found in genes (or in their close proximity) linked to the previously revealed KTCN-specific cellular components, namely, "Actin cytoskeleton", "Extracellular matrix", "Collagen-containing extracellular matrix", "Focal adhesion", "Hippo signaling pathway", and "Wnt signaling" pathways. No genomic heterogeneity across the corneal surface was found comparing the assessed
Conclusion
The identified genomic features indicate the involvement of innate and adaptive immune system responses in KTCN pathogenesis.
Identifiants
pubmed: 37483635
doi: 10.3389/fimmu.2023.1197054
pmc: PMC10359427
doi:
Substances chimiques
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1197054Informations de copyright
Copyright © 2023 Jaskiewicz, Maleszka-Kurpiel, Kabza, Karolak and Gajecka.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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