Abstract
Purpose:
To identify early biomarkers of retina macroglia activation in diabetic patients without and with nonproliferative diabetic retinopathy.
Methods:
22 diabetic subjects with mild or moderate non proliferative diabetic retinopathy (NPDR) were enrolled and 12 healthy subjects served as controls. All eyes had cataract of the same score according to LOCS classification. Twelve diabetic patients had no signs of diabetic macular edema (DR-noDME), and 10 had DME (DR-DME). Aqueous humor was sampled in all eyes using a 30 gauge needle through a peripheral clear cornea approach, before cataract extraction. Each subject underwent full ophthalmic examination and Spectral Domain Optical Coherence Tomography (SD-OCT) before aqueous humor sampling. Each sample was analyzed to quantify: glial fibrillary acidic protein (GFAP), aquaporine 1 (AQP1) and AQP4 as biomarkers of retinal macroglial activity, by ELISA. ANOVA analysis followed by Tukey-Kramer post-hoc test was applied.
Results:
There was not significant difference in the age among the four groups. Mean concentration of GFAP, AQP1 and AQP4 significantly increased in diabetic eyes versus controls (324.44±262.54 pg/µg vs 182.34±114.44 pg/µg for GFAP; 105.72±15.69 pg/µg vs 50.92±20.36 pg/µg for AQP1; and 852.03+103.24 pg/µg vs 33.58±21.20 pg/µg for AQP4; p<0.005, for each comparison). GFAP showed an approximate 0.8 fold increase, AQP1 1.1 fold increase, whereas AQP4 about 24 folds increase in diabetic patients versus controls. When DR-noDME eyes and DR-DME eyes were separately evaluated, there was a significant decrease in GFAP, AQP1 e AQPR in DR-DME eyes versus DR-noDME eyes, (Tukey Kramer post hoc p<0.05). GFAP and AQP1 showed even a slight, non significant, fold decrease versus controls. AQP4/AQP1 concentration showed weak and non significant correlation (Tau=0.21, p=0.3) between these biomarkers, despite increasing trend.
Conclusions:
GFAP, AQP1 and AQP4 are known as biomarkers of retinal macroglia activity. All these biomarkers are significantly increased in human eyes with diabetes, confirming that retinal glia is a key actor in this disorder. The decrease of these biomarkers In eyes with DME probably represents a sign of Müller cells degeneration.
Keywords: 499 diabetic retinopathy •
699 retinal glia •
427 aqueous