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Min Zhao, Elodie Bousquet, Jean-Claude Jeanny, Patricia Lassiaz, Francine F Behar-Cohen; Expression of Water/ion Channels and Inflammatory Markers in the Retina of Goto-Kakizaki Type 2 Diabetic Rat: Contribution of Mineralocorticoid Receptor Pathway. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5823.
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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. We aimed to evaluate the expression of water/ion channels and inflammatory state in diabetic retina using Goto-Kakizaki (GK) type 2 diabetic rat, and to investigate an eventual contribution of MR pathway in the development of DME.
Three- and 6-month old GK rats were used to compare their retinal morphology to age-matched wistar rats. Expression of MR, potassium channel Kir4.1, aquaporins (AQP) and inflammatory markers was assessed using quantitative PCR. Immunolocalization of Kir4.1 and AQP4, activation of retinal Müller glial (RMG) and microglial cells were also investigated.
We observed an up-regulation of MR, Kir4.1, AQP9, cyclooxygenase 2, interleukin 1 beta (IL1β), IL6 and MR specific marker neutrophil gelatinase-associated lipocalin in both 3 and 6 months GK rats compared to age-matched wistar rats. AQP4 transcripts did not change at both ages, while AQP1 was increased only at 6 months. Immunostaining showed perivascular enhancement of Kir4.1 and AQP4 and their localization towards the retinal outer limiting membrane in GK rats of 3 months. At 6 months, we observed a decrease in Kir4.1 and AQP4 in vascular processes. Round activated microglial cells were observed in the outer retina of GK rats of 3 months. RMG cells were also activated in GK rats at 3 months. GK rats showed choroidal vasodilation, focal thickening of photoreceptor segments and adjacent retinal pigment epithelial cell swelling. At 6 months, minor serous retinal detachment was observed in GK rats.
Altered expression of water/ion channels and pro-inflammatory state in the retina of GK diabetic rat disturb the retinal fluid homeostasis, leading to fluid accumulation in the outer retina. Over expression of MR and its specific marker in diabetic retina indicates probable contribution of MR pathway, which should be further confirmed using MR antagonist.
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