Aqueous Humor Biomarkers of Muller Cell Activation in Diabetic Eyes

PURPOSE. To identify early biomarkers of retinal Muller cell activation in diabetic eyes with or without clinically detectable signs of diabetic retinopathy (DR). METHODS. This study was a cross-sectional comparative case series. The aqueous humor (AH) of 34 eyes was collected in 12 healthy controls, 11 diabetic patients without DR, and 11 diabetic patients with nonproliferative DR. Full ophthalmic examination and spectral-domain optical coherence tomography were performed in all eyes. Glial fibrillary acidic protein (GFAP), aquaporin 1 (AQP1), and aquaporin 4 (AQP4) were quantified in AH samples as biomarkers of Muller cell activity by ELISA. Statistical analysis was performed with ANOVA followed by Tukey-Kramer post hoc test. RESULTS. There was no significant difference in the age among the three groups. Mean concentration of GFAP, AQP1, and AQP4 significantly increased in diabetic eyes versus controls (P < 0.05, for each comparison). Glial fibrillary acidic protein and AQP1 showed an approximate 2-fold increase, whereas AQP4 showed an approximate 25-fold increase in diabetics with DR versus controls. In diabetics without DR, AQP4 showed an approximate 6-fold increase versus controls. CONCLUSIONS. Glial fibrillary acidic protein, AQP1, and AQP4-biomarkers of Muller cell activity-are significantly increased in human eyes with diabetes, confirming that Muller cells are precociously affected by diabetes mellitus.