Common and Distinct Features in Serum Proteomic Profiles in Keratoconus, Post-Laser Vision Correction Ectasia, and Pellucid Marginal Degeneration.

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.