ArticleInvestigative ophthalmology & visual science2025
Inter-Eye Molecular Discrepancies in the Corneal Epithelium Point to TFRC in the Keratoconus Severity Signature and Mechanism of Cone Formation.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Common and Distinct Features in Serum Proteomic Profiles in Keratoconus, Post-Laser Vision Correction Ectasia, and Pellucid Marginal Degeneration.Investigative ophthalmology & visual science · 2026Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: There is no molecular evidence available confirming or contradicting inter-eye molecular variability in keratoconus (KTCN). The key question is whether the use of a model of more and less affected eyes of the same pair facilitates the identification of specific molecular features of KTCN severity. Methods: This retrospective case-control study involved 21 KTCN patients (n = 132 experimental samples derived from 42 corneal epithelium samples separated into central, middle, and peripheral topographic regions) analyzed in the paired model. Transcriptomic (RNA-sequencing) and proteomic (MALDI-TOF/TOF MS/MS) profiling was performed. An additional non-paired model, including KTCN patients (n = 42) and controls (n = 14), strengthened the assessment. Then, key findings were validated in a rediscovery study with 20 patients using reverse-transcription quantitative polymerase chain reaction, immunofluorescence staining, and confocal microscopy. Results: In the paired model, which included patients with ≥1 grade difference in topographic keratoconus classification, 48 differentially expressed genes were identified. Over-representation analysis highlighted the GO term "cell-cell adhesion" (adjusted P = 0.028), with key contributors including ACTN1, EPCAM, PCDH19, PVR, and TFRC. TFRC showed significantly higher expression in the middle topographic region of more severely affected eyes (P = 0.008, paired t-test), correlating with the average topographic region thickness (R = 0.53, P = 0.008) and flat keratometry (K1; R = 0.49, P = 0.016). Immunofluorescence confirmed intra-individual and regional differences in transferrin receptor (TFRC) protein expression, with increased expression in the middle topographic region of more advanced eyes, compared to eyes with forme fruste KTCN. Conclusions: Inter-eye variability implicates TFRC as a component of the KTCN severity signature, thus adding the element to the mechanisms underlying KTCN cone formation.
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