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Maria E Marin Castano, Marco Ruggeri, Delia DeBuc, Fernando Penha, Xiang-Run Huang, Retina; Modification in the retinal nerve fiber layer thickness and microtubule-associated proteins (MAPs) expression in diabetic mice.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4910.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is the most common complication in diabetes and the leading cause of adult blindness. DR was considered primarily a retinal microvascular disorder. However, retinal neurodegeneration is present even before the development of clinically detectable microvascular damage and may, therefore, represent an early event in the pathophysiology of DR. The retinal nerve fiber layer (RNFL), consists of the axons of retinal ganglion cell (RGC) which have a remarkable system of proteins and filaments that constitute axonal cytoskeleton. Moreover, the cytoskeleton filaments are connected to one another by microtubule-associated proteins (MAPs). Loss of RGCs and their axons resulting in RNFL thinning has been detected in diabetic eyes. However, to date, there is lack of knowledge about the underlying mechanisms leading to RNFL damage under the diabetic conditions. The purpose of this study was to determine RNFL thickness and distortion of cytoskeletal components in order to understand how diabetes acts at a cellular level in the retina.
Ten C57BL/6 male mice were divided into 2 groups (n = 5). To induce diabetes, animals (Group 1) received daily intraperitoneal injections of STZ (50 mg/kg of body weight) for 5 days. Control animals (Group 2) were injected with citrate buffer only. Seven days after the fifth injection, animals were weighed and the blood glucose levels measured using a glucomonitor. Tail vein blood was used for blood glucose analyses. Mice with glucose levels above 300-400 mg/dl were considered as hyperglyceamic. Body weight and blood glucose were recorded at one-week intervals. At 6 weeks after STZ treatment, fundus photography (FP) and OCT were performed. OCT images were segmented and the RNFL thickness was calculated. Then, animals were sacrificed and retinas collected for protein extraction and quantification. MAPs (MAP1A and MAP2) protein expression was determined by Western blot.
We found that at 6 weeks after induction of diabetes, diabetic mice showed reduced RNFL thickness in the pericentral and peripheral regions without abnormalities in the FP. Moreover, we found a decrease in the MAP1A and MAP2 expression in retinas from diabetic mice.
The observed phenomenon may be due to modification of cytoskeleton’s ultrastructure which could be an early event of the neurodegenerative process in early DR.
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