SERSome-based metabolic profiling of aqueous humor for cataract subtyping with molecule-level interpretability

Area of Science:

• Ophthalmology
• Analytical Chemistry
• Biochemistry

Background:

• Cataract is a major cause of vision impairment globally, necessitating subtype-specific treatments.
• Current diagnostic methods lack the molecular-level detail required for personalized cataract care.
• Surface-enhanced Raman spectroscopy (SERS) offers sensitive, compact, and clinically adaptable molecular fingerprinting.

Purpose of the Study:

• To develop an integrated, robust, and interpretable methodology for metabolic profiling of aqueous humor for cataract subtyping.
• To establish a SERS-based approach for rapid and accurate identification of cataract-associated metabolites.
• To provide a scalable tool for both fundamental research and clinical applications in eye diseases.

Main Methods:

• Developed a two-step sample pretreatment protocol for efficient metabolite extraction compatible with SERS detection.
• Employed the SERSome strategy for rapid and robust metabolic profiling of aqueous humor.
• Utilized molecule-level SERSome interpretation by correlating intra-correlation networks with metabolite SERS barcodes.
• Applied statistical comparison, interpretable machine learning, and association analysis for biomarker identification.

Main Results:

• Successfully established a systematic methodology for metabolic analysis of aqueous humor using SERS.
• Identified key metabolite biomarkers, including ergothioneine, hypoxanthine, and uric acid, associated with cataract subtyping.
• Demonstrated the association of these biomarkers with cataract and diabetic retinopathy, showcasing diagnostic potential.
• Validated the SERSome strategy for rapid, cost-efficient, and scalable metabolic profiling.

Conclusions:

• The developed SERS-based methodology provides a powerful tool for metabolic profiling of aqueous humor, aiding in cataract subtyping.
• Identified metabolite biomarkers offer potential for early diagnosis and personalized treatment strategies for cataracts and related conditions.
• This integrated approach is highly suitable for clinical adoption and applicable to various diseases requiring metabolic analysis.