September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The contribution of RPE-specific insulin signaling to the development of outer retina dysfunction associated with diabetes.
Author Affiliations & Notes
  • Ivy S Samuels
    Research Service, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, United States
    Dept of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Alecia H. Cutler
    Dept of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Matthew J. Tarchick
    Research Service, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, United States
    Dept of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Bela Anand-Apte
    Dept of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Ivy Samuels, None; Alecia Cutler, None; Matthew Tarchick, None; Bela Anand-Apte, None
  • Footnotes
    Support  This work was supported by a Career Development award to ISS from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, a VA Merit Award i01-BX002754 from Biomedical Laboratory Research and Development to ISS, NIH R01EY020861 to BAA and an unrestricted grant from the Research to Prevent Blindness to the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5422. doi:
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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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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