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Michael J Allingham, Nomingerel Tserentsoodol, Peter Saloupis, Scott W Cousins; Low dose aldosterone exposure causes increased retinal edema following laser-induced retinal vein occlusion in mice.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3669.
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The pathobiology of retina edema (RE) is incompletely understood. Mechanistic studies are limited by the lack of physiologic animal models. We have developed a model of RE based on laser-induced vein occlusion (RVO) in order to determine the role of the mineralocorticoid receptor in RE pathobiology.
RVO was induced immediately following intravenous injection of rose bengal (60mg/kg) using a 532 nm wavelength laser to place 3-7 applications at 80 mW and 50 micron spot size directed at the superior retinal vein one disc diameter away from the nerve. Negative control consisted of placing an equal number of laser spots without targeting the vein. Male and female C57BL/6J mice aged 7-9 months with confirmed absence of Crb1rd8 were used. Aldosterone pellets releasing a daily dose of 1 ug/d were implanted subcutaneously 4 weeks prior to RVO. Retinal imaging by optical coherence tomography (OCT) was performed using a Micron 4 rodent imaging system. Retinas were analyzed by immunohistochemistry using standard techniques. Retinal imaging and tissue analysis were performed 2, 4 and 7 days following RVO. Comparisons were made using Pearson’s Chi Square and Wilcoxon Rank Sum testing.
RE in the form of cystic spaces and retinal thickening was evident both by OCT and by histology. Following standard RVO, RE present on OCT in 88% of eyes at day 2, 38% of eyes at day 4 and 0% of eyes at day 7 (n=8). By comparison, in aldosterone treated eyes, RE was present in 100% of eyes at day 2 and 4 and 50% of eyes at day 7 (n=8). This difference was statistically significant at day 4 (p=0.007) and day 7 (p=0.02). Maximal retinal thickness was higher at day 2 in aldosterone treated mice 1.85 vs 1.27 (p=0.04). Histologically, areas of edema demonstrate increased macrophage infiltration, Muller cell activation and redistribution of aquaporin 4 and Kir4.1 channels. These findings were more severe in aldosterone treated mice. No RE or changes in Muller cell markers were seen in negative controls.
RVO creates mild to moderate RE which resolves spontaneously. Activation of the MR by systemic low dose aldosterone significantly enhances the severity and duration of RE following RVO and this is associated with macrophage infiltration and Muller cell dysfunction. MR may play a role in pathogenesis of macular edema in RVO and possibly other forms of macular edema.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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