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Edoardo Midena, Silvia Bini, Marianna Berton, Alessandra Micera, Graziana Esposito, Raffaele Parrozzani, Stela Vujosevic; Müller Cells Changes in Diabetic Macular Edema: in vivo Correlation between OCT and Molecular Biomarkers in Human Diabetics. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4429.
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© ARVO (1962-2015); The Authors (2016-present)
To correlate specific biomarkers of Müller cells activation with Spectral Domain OCT (SD-OCT) findings in diabetic patients with and without diabetic macular edema (DME).
Twenty-six diabetic subjects with mild or moderate non proliferative diabetic retinopathy were enrolled and 14 healthy subjects served as controls. Twelve diabetic patients had no signs of DME (no DME group), and 14 had DME (DME group). Aqueous humor was sampled in all eyes using a 30 gauge needle through a peripheral clear cornea approach. Each subject underwent full ophthalmic examination, and SD-OCT individual retinal layers segmentation before aqueous humor sampling. Each sample was analyzed to quantify: glial fibrillary acidic protein (GFAP), aquaporine 1 (AQP1) and AQP4 as biomarkers of Müller cells activation, by ELISA. ANOVA analysis followed by Tukey-Kramer post-hoc test was applied. Retinal layering was performed at least twice, by two independent, masked examiners.
There was not significant difference in mean age among the three groups. Mean concentration of GFAP, AQP1 and AQP4 significantly increased in diabetic eyes versus controls (p<0.002, for each comparison). In particular, AQP4 showed a 25 folds increase in diabetic patients versus controls. When no DME eyes were compared to DME eyes, a significant decrease in GFAP, AQP1 e AQPR in DME eyes versus no DME eyes (p<0.05) was also documented. However, Müller cells biomarkers never reached normal values in DME eyes (p<0.05, vs controls) When biomarkers quantification was compared with SD-OCT layering, a significant increase of INL + OPL layers was documented in eyes with (associated with cystic changes) and without DME versus controls (vs controls p<0.001). The inter-grader agreement was at least substantial for all SD-OCT measurements.
The activation of Müller cells in diabetic retina is confirmed by the increase of specific biomarkers, even in the aqueous humor. Müller cell activation shows a direct relationship with the increase in thickness of retinal layers where Müller cells are resident. The decrease of the specific biomarkers in eyes with DME, associated with cystic changes in the middle retina, probably represents a sign of Müller cells degeneration. These data underline the opportunity of earlier treatment of DME, before Müller cells degeneration develops..
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