Cross-Compartment Proteomic Signatures in Human Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Area of Science:

• Ophthalmology
• Proteomics
• Molecular Biology

Background:

• Diabetic retinopathy (DR) is a primary cause of preventable blindness.
• Its molecular basis involves complex changes across multiple biological systems.
• Identifying consistent molecular signatures is crucial for understanding DR pathophysiology.

Purpose of the Study:

• To systematically review and meta-analyze proteomic findings in human DR studies.
• To identify consistent molecular signatures across different biological compartments in DR.
• To evaluate the potential for clinical translation of these proteomic findings.

Main Methods:

• Systematic review and meta-analysis following PRISMA guidelines.
• Inclusion of 28 studies analyzing proteomic data from vitreous, aqueous, plasma, tears, and urine.
• Standardization of proteomic results and use of random-effects multilevel models for synthesis.

Main Results:

• Overall protein upregulation observed in DR.
• Consistent and robust upregulation of fibrinogen chains (FGA, FGB, FGG) across ocular compartments.
• Identification of vitronectin, RBP4, prothrombin, and afamin as potential stage-specific biomarkers.

Conclusions:

• This study provides the first integrated proteomic analysis across multiple compartments in DR.
• Fibrinogen chains are consistently upregulated in the eye, serving as a key molecular signature.
• The findings establish a strong evidence base for biomarker validation and clinical translation in DR management.