Untargeted Tear Proteomics in Keratoconus
Investigative Ophthalmology & Visual Science (IOVS), 2025
This study investigated molecular changes in the tear fluid of individuals with keratoconus (KC) using a large South-Asian cohort to identify proteins and pathways that differ across disease stages.
Researchers analyzed tear samples from 40 healthy individuals and 107 eyes with varying KC grades using untargeted mass spectrometry (iTRAQ-based LC-MS/MS) to profile proteins without prior assumptions.
Key Findings:
A total of 1104 tear proteins were identified, and 279 were quantified across samples.
Thirty-two proteins showed significant changes in expression in KC patients compared with controls, indicating dysregulation of biological processes.
Dysregulated proteins were involved in:
Glycolytic and metabolic pathways, suggesting altered cellular metabolism in KC.
Extracellular matrix (ECM) organization, consistent with the corneal structural weakening seen in KC.
Reactive oxygen species (ROS) detoxification and inflammatory regulation, highlighting oxidative stress and immune involvement in disease progression.
Several proteins such as Cystatin-S, Lacritin, Glutathione Synthetase, and Superoxide Dismutase were validated to show differential expression across KC grades, pointing to potential biomarkers for disease severity.
Conclusions:
These results reveal novel tear fluid proteins and pathways associated with keratoconus progression, including inflammatory signaling, ECM remodeling, and metabolic alterations. The study’s findings improve understanding of the molecular mechanisms underlying KC and may guide the development of stage-specific biomarkers and therapeutic targets.