Tear nanoDSF Denaturation Profile Is Predictive of Glaucoma

Area of Science:

• Ophthalmology
• Biomarker Discovery
• Proteomics

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness.
• Early detection and treatment are crucial for preserving visual function but are hindered by asymptomatic early stages and lack of objective diagnostics.
• Tear fluid (TF) contains potential biomarkers, but multi-omics analysis is complex for clinical use.

Purpose of the Study:

• To investigate a novel concept for glaucoma diagnostics using rapid high-performance analysis of the tear fluid proteome.
• To evaluate differential scanning fluorimetry (nanoDSF) for identifying glaucoma-specific protein denaturation profiles in TF.
• To assess the potential of TF denaturation profiles as a non-invasive biomarker for POAG screening.

Main Methods:

• Collected tear fluid (TF) from 311 ophthalmic patients.
• Analyzed TF protein thermal denaturation profiles using nanoDSF.
• Applied clustering and machine learning algorithms to identify glaucoma-associated profiles.
• Quantified specific TF proteins and identified low-molecular-weight ligands.

Main Results:

• Distinct TF protein denaturation profiles with characteristic peak shifts were observed in POAG patients.
• Clustering identified glaucoma in 70% of cases; machine learning reduced false positives to 13.5%.
• POAG-associated TF alterations included increased serum albumin and decreased lysozyme C, lipocalin-1, and lactotransferrin, influenced by ligands like fatty acids and iron.

Conclusions:

• The TF denaturation profile serves as a novel, integrated biomarker for glaucoma, reflecting proteomic, lipidomic, and metallomic changes.
• This non-invasive method, analyzing TF protein denaturation, shows potential for rapid clinical screening of POAG.
• Monitoring TF denaturation profiles could significantly improve early disease detection and management.