Investigative ophthalmology & visual science · 2026
Common and Distinct Features in Serum Proteomic Profiles in Keratoconus, Post-Laser Vision Correction Ectasia, and Pellucid Marginal Degeneration.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Jaskiewicz-Rajewicz Katarzyna, Wysocka Alicja, Matuszewska-Mach Eliza, Rzetecka Natalia, Maleszka-Kurpiel Magdalena, Wozniak Jakub, Michalski Andrzej, Udziela Monika, Szaflik Jacek P, Ploski Rafal, Rydzanicz Malgorzata, Matysiak Jan, Gajecka Marzena
Аннотация
PURPOSE: Both intrinsic and extrinsic factors are implicated in keratoconus (KTCN), pellucid marginal degeneration (PMD), and post-laser vision correction (PLVC) ectasia etiology. Serum proteomic profiling was performed to molecularly differentiate the ectasia and to assess systemic components in their pathophysiology.
METHODS: Serum samples from 93 patients with KTCN, 10 patients with PLVC, 4 patients with PMD, and 44 non-ectatic controls were profiled using matrix-assisted laser desorption ionization-time of flight tandem mass spectrometry (MALDI-TOF/TOF MS/MS). Clinical and environmental variables (e.g. allergy/atopy/asthma and eye rubbing intensity), together with ophthalmologic parameters (K1, K2, Kmax, TCT, and anterior/posterior elevation), were assessed in the principal component analysis (PCA), Weighted Gene Co-expression Network Analysis (WGCNA), linear modeling, and other assessments. Serum m/z features were correlated with RNA-seq data from corneal epithelium (CE) samples of 31 individuals.
RESULTS: As findings of the PCA, associations were observed for atopy and/or asthma (estimate = -5.52, P = 0.03), PMD diagnosis (estimate = 8.3, P = 0.04), and age (estimate = -0.14, P = 0.01), with observable trends for KTCN status and intense eye rubbing. Correlations between clinical variables and individual m/z features indicated that posterior elevation, reflecting KTCN severity, was associated with an ATP5B protein-assigned peak (m/z 1921.9655, ρ = -0.31, adjusted P = 0.016). In the integration analyses, correlations between serum peaks and corresponding CE gene expression, including APOH- (ρ = 0.43, P = 0.017) and ALB-assigned peaks (ρ = 0.35-0.42, P < 0.05) were identified. Pairwise eigengene comparisons showed negative correlation between KTCN and non-ectatic controls (Pearson r = -0.89, P = 0.007).
CONCLUSIONS: The local ocular pathology is reflected in serum proteomic profiles, together with accompanying systemic inflammation and intense eye-rubbing behavior. Common proteomic features of different types of corneal ectasia may reflect overlapping pathophysiological mechanisms.
METHODS: Serum samples from 93 patients with KTCN, 10 patients with PLVC, 4 patients with PMD, and 44 non-ectatic controls were profiled using matrix-assisted laser desorption ionization-time of flight tandem mass spectrometry (MALDI-TOF/TOF MS/MS). Clinical and environmental variables (e.g. allergy/atopy/asthma and eye rubbing intensity), together with ophthalmologic parameters (K1, K2, Kmax, TCT, and anterior/posterior elevation), were assessed in the principal component analysis (PCA), Weighted Gene Co-expression Network Analysis (WGCNA), linear modeling, and other assessments. Serum m/z features were correlated with RNA-seq data from corneal epithelium (CE) samples of 31 individuals.
RESULTS: As findings of the PCA, associations were observed for atopy and/or asthma (estimate = -5.52, P = 0.03), PMD diagnosis (estimate = 8.3, P = 0.04), and age (estimate = -0.14, P = 0.01), with observable trends for KTCN status and intense eye rubbing. Correlations between clinical variables and individual m/z features indicated that posterior elevation, reflecting KTCN severity, was associated with an ATP5B protein-assigned peak (m/z 1921.9655, ρ = -0.31, adjusted P = 0.016). In the integration analyses, correlations between serum peaks and corresponding CE gene expression, including APOH- (ρ = 0.43, P = 0.017) and ALB-assigned peaks (ρ = 0.35-0.42, P < 0.05) were identified. Pairwise eigengene comparisons showed negative correlation between KTCN and non-ectatic controls (Pearson r = -0.89, P = 0.007).
CONCLUSIONS: The local ocular pathology is reflected in serum proteomic profiles, together with accompanying systemic inflammation and intense eye-rubbing behavior. Common proteomic features of different types of corneal ectasia may reflect overlapping pathophysiological mechanisms.