Current eye research · 2026
Cross-Compartment Proteomic Signatures in Human Diabetic Retinopathy: A Systematic Review and Meta-Analysis.
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Behera Soumya, Sahoo Nibedita, Sahu Subhangi
Аннотация
PURPOSE: Diabetic retinopathy (DR) is a leading cause of preventable blindness, with complex molecular pathophysiology spanning multiple biological compartments. This systematic review and meta-analysis aimed to synthesize proteomic findings from human DR studies to identify consistent cross-compartment molecular signatures and evaluate their clinical translation potential.
METHODS: Following a prespecified PRISMA protocol, we searched databases and registries to September 2025. Two reviewers independently screened, extracted, and assessed risk of bias using validated tools. Proteomic results were standardized to log2 fold-change (Log2FC) with reconstructed SEs where necessary. Random-effects multilevel models (REML) incorporated protein- and study-level variance. Prespecified subgroup analyses (aqueous, vitreous, plasma), meta-regression (compartment, protein family, interactions), and diagnostics (Egger's test, trim-and-fill, leave-one-out) probed robustness. Qualitative synthesis integrated 28 eligible studies across vitreous, aqueous, plasma/serum, tears, and urine.
RESULTS: Twenty-eight studies contributed data. Quantitative synthesis showed overall protein upregulation in DR (Log2FC = 1.49; 95% CI: 0.72-2.27). Subgroup analyses demonstrated strong and consistent effects in vitreous (Log2FC = 2.41) and aqueous (1.28 humors, with plasma estimates weaker and more heterogeneous. Fibrinogen chains (FGA, FGB, FGG) were robustly upregulated across compartments and exceeded complement proteins (β = +1.41; p < 0.001). Publication-bias adjustment (trim-and-fill, k0 = 5) yielded a reduced but still significant effect (Log2FC = 1.10). Qualitative evidence highlighted vitronectin, RBP4, prothrombin, and afamin as additional stage-specific candidates, while tear- and urine-based markers showed potential for noninvasive screening.
CONCLUSION: This first integrated systematic review and meta-analysis of multicompartment proteomic studies in diabetic retinopathy shows consistent upregulation of fibrinogen chains across ocular compartments, highlights vitronectin and stage-specific proteins as additional candidates, and establishes a rigorous evidence base to guide biomarker validation and clinical translation.
METHODS: Following a prespecified PRISMA protocol, we searched databases and registries to September 2025. Two reviewers independently screened, extracted, and assessed risk of bias using validated tools. Proteomic results were standardized to log2 fold-change (Log2FC) with reconstructed SEs where necessary. Random-effects multilevel models (REML) incorporated protein- and study-level variance. Prespecified subgroup analyses (aqueous, vitreous, plasma), meta-regression (compartment, protein family, interactions), and diagnostics (Egger's test, trim-and-fill, leave-one-out) probed robustness. Qualitative synthesis integrated 28 eligible studies across vitreous, aqueous, plasma/serum, tears, and urine.
RESULTS: Twenty-eight studies contributed data. Quantitative synthesis showed overall protein upregulation in DR (Log2FC = 1.49; 95% CI: 0.72-2.27). Subgroup analyses demonstrated strong and consistent effects in vitreous (Log2FC = 2.41) and aqueous (1.28 humors, with plasma estimates weaker and more heterogeneous. Fibrinogen chains (FGA, FGB, FGG) were robustly upregulated across compartments and exceeded complement proteins (β = +1.41; p < 0.001). Publication-bias adjustment (trim-and-fill, k0 = 5) yielded a reduced but still significant effect (Log2FC = 1.10). Qualitative evidence highlighted vitronectin, RBP4, prothrombin, and afamin as additional stage-specific candidates, while tear- and urine-based markers showed potential for noninvasive screening.
CONCLUSION: This first integrated systematic review and meta-analysis of multicompartment proteomic studies in diabetic retinopathy shows consistent upregulation of fibrinogen chains across ocular compartments, highlights vitronectin and stage-specific proteins as additional candidates, and establishes a rigorous evidence base to guide biomarker validation and clinical translation.