ArticlePloS one2022
Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Construction and characteristics of an adjustable biomechanical in vitro corneal stromal model simulating keratoconus pathological features.Materials today. Bio · 2025Article
- The microenvironment of ocular surface in keratoconus: a systematic review.Eye and vision (London, England) · 2025Review
- Systematic Ocular Phenotyping of Knockout Mouse Lines Identifies Genes Associated With Age-Related Corneal Dystrophies.Investigative ophthalmology & visual science · 2025Article
- Machine Learning-Driven Transcriptome Analysis of Keratoconus for Predictive Biomarker Identification.Biomedicines · 2025Article
- Omics in Keratoconus: From Molecular to Clinical Practice.Journal of clinical medicine · 2025Review
- Expression Distribution of Keratins in Normal and Pathological Corneas and the Regulatory Role of Krt17 on Limbal Stem Cells.Investigative ophthalmology & visual science · 2025Article
- Single-Cell Multiomics Analysis of Early Wound Response Programs in the Mouse Corneal Epithelium.Investigative ophthalmology & visual science · 2025Article
- Modeling Neuropathic Corneal Pain: Pulled Nerve Approach With Elevated Krt16 Gene Expression.Investigative ophthalmology & visual science · 2025Article
- Tear proteomic analysis in keratoconus patients and potential biomarkers: a case-control study.Experimental biology and medicine (Maywood, N.J.) · 2025Observational
- Rutin-Activated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Attenuates Corneal and Heart Damage in Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Proteomic Characterization of Corneal Epithelial and Stromal Cell-Derived Extracellular Vesicles.International journal of molecular sciences · 2024Article
- Identification of hub genes and molecular pathways in keratoconus by integrating bioinformatics and literature mining at the RNA level.International ophthalmology · 2024Article
- Balanced activation of Nrf-2/ARE mediates the protective effect of sulforaphane on keratoconus in the cell mechanical microenvironment.Scientific reports · 2024Article
- Oxidative Stress and Cellular Protein Accumulation Are Present in Keratoconus, Macular Corneal Dystrophy, and Fuchs Endothelial Corneal Dystrophy.Journal of clinical medicine · 2023Article
- A Kaleidoscope of Keratin Gene Expression and the Mosaic of Its Regulatory Mechanisms.International journal of molecular sciences · 2023Review
- Role of Oxidative Stress in Ocular Diseases: A Balancing Act.Metabolites · 2023Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keratoconus (KC) is a multifactorial progressive ectatic disorder characterized by local thinning of the cornea, leading to decreased visual acuity due to irregular astigmatism and opacities. Despite the evolution of advanced imaging methods, the exact etiology of KC remains unknown. Our aim was to investigate the involvement of corneal epithelium in the pathophysiology of the disease. Corneal epithelial samples were collected from 23 controls and from 2 cohorts of patients with KC: 22 undergoing corneal crosslinking (early KC) and 6 patients before penetrating keratoplasty (advanced KC). The expression of genes involved in the epidermal terminal differentiation program and of the oxidative stress pathway was assessed by real time PCR analysis. Presence of some of the differentially expressed transcripts was confirmed at protein level using immunofluorescence on controls and advanced KC additional corneal samples. We found statistically significant under-expression in early KC samples of some genes known to be involved in the mechanical resistance of the epidermis (KRT16, KRT14, SPRR1A, SPRR2A, SPRR3, TGM1 and TGM5) and in oxidative stress pathways (NRF2, HMOX1 and HMOX2), as compared to controls. In advanced KC samples, expression of SPRR2A and HMOX1 was reduced. Decreased expression of keratin (KRT)16 and KRT14 proteins was observed. Moreover, differential localization was noted for involucrin, another protein involved in the epidermis mechanical properties. Finally, we observed an immunofluorescence staining for the active form of NRF2 in control epithelia that was reduced in KC epithelia. These results suggest a defect in the mechanical resistance and the oxidative stress defense possibly mediated via the NRF2 pathway in the corneal keratoconic epithelium.
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