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Min Zhao, Charlotte Andrieu-Soler, elodie bousquet, Rinath Levy, Francisco Halili, Alejandro Arboleda, Esther Rodríguez-Villagra, Irene Bravo-Osuna, Rocio Herrero-Vanrell, Francine F Behar-Cohen; Effects of Mineralocorticoid Receptor Antagonist on Diabetic Retina Using Goto-Kakizaki Rat. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2271.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic macular edema (DME) is the leading cause of blindness in the diabetic population. However, its mechanism is not fully understood. We previously showed that, in the normal rat eye, activation of mineralocorticoid receptor (MR) deregulates retinal water/ion channels, leading to retinal swelling. In diabetic patients, MR antagonism improves insulin sensitivity and reduces albuminuria. We aimed to investigate the effects of MR antagonist in diabetic retina using Goto-Kakizaki (GK) type 2 diabetic rat.
Spironolactone was loaded in poly(lactide-co-glycolide) (PLGA, lactide:glycolide 50:50) microspheres. Three-month old diabetic GK rats and age-matched control Wistar rats were used. Non-loaded or spironolactone-loaded microspheres were injected intravitreously (IVT) in the rat eye. Glycemia and glycated hemoglobin (HbA1c) were measured before and 1 month after IVT. At 1 month, animals were sacrificed, eyes removed for histological analysis. Expression of MR, water/ion channels, inflammatory markers, and angiogenic factors was also assessed in the neuroretina using quantitative PCR.
The PLGA microspheres allowed sustained release of spironolactone for 1 month. Glycemia and HbA1c were more elevated in GK than in Wistar rats. Intravitreous spironolactone had no effect on glycemia or HbA1c level. GK rats showed choroidal vasodilation that was reduced by spironolactone. We observed an up-regulation of MR, AQP9, cyclooxygenase 2, interleukin 18 (IL18), neutrophil gelatinase-associated lipocalin (Ngal) and placental growth factor (PGF) in GK rats compared to Wistar rats. Among those, spironolactone significantly reduced the expression of Ngal, IL18 and PGF in GK rats.
GK diabetic rat shows altered retinal morphology and over-expression of MR, water channels, pro-inflammatory markers and angiogenic factors. MR antagonist reduces Ngal, IL18 and PGF transcripts and improves the retinal morphology, suggesting a MR role in the diabetic retina. The therapeutic potential of MR antagonist for diabetic retinopathy is worth further investigation.
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