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Ivy S Samuels, Alecia H. Cutler, Matthew J. Tarchick, Bela Anand-Apte; The contribution of RPE-specific insulin signaling to the development of outer retina dysfunction associated with diabetes.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5422.
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© ARVO (1962-2015); The Authors (2016-present)
Analysis of the Wisconsin Epidemiological Study of Diabetic Retinopathy demonstrated that type 2 diabetic patients undergoing insulin treatment for ≥10 years exhibited significantly higher risk of macular edema compared to patients without insulin treatment within 6 months of the time of analysis. Mouse models of either type 1 or type 2 diabetes displayed RPE dysfunction at very early times following onset of hyperglycemia. As the RPE constitutes the outer blood retinal barrier and mouse models of diabetes treated with insulin also displayed breakdown of the blood retinal barrier, we sought to determine if insulin signaling specifically within the RPE contributed to functional and structural RPE defects associated with diabetic retinopathy and biomarkers of diabetic macular edema.
The insulin receptor (IR) was conditionally inactivated in the RPE by breeding mice expressing a floxed IR with the Best1-cre mouse. Mice were made diabetic by injection with streptozotocin and analysis was performed 2 or 4 weeks following onset of diabetes. RPE structure was evaluated by analysis of semi-thin sections. Tight junction integrity was interrogated by ZO-1 staining of RPE flatmounts. Insulin signaling was measured by western blot analysis of RPE lysate and RPE and retina function were measured by electroretinography.
Loss of insulin signaling the RPE exacerbated defects in the ERG of diabetic mice. Histological parameters including RPE thickness, tight junction integrity and parameters of insulin signaling were analyzed.
Modulation of insulin signaling in the RPE may be a valid therapeutic target in prevention of the earliest signs of diabetic retinopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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