Investigative Ophthalmology & Visual Science Cover Image for Volume 59, Issue 9
July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Systemic reduction of GLUT1 prevents hallmarks of diabetic retinopathy
Author Affiliations & Notes
  • Ivy S Samuels
    Research Service, Louis Stokes VA Medical Center, Cleveland Heights, Ohio, United States
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Matthew Tarchick
    Research Service, Louis Stokes VA Medical Center, Cleveland Heights, Ohio, United States
    Biology, University of Akron, Akron, Ohio, United States
  • Timothy D. Trobenter
    Research Service, Louis Stokes VA Medical Center, Cleveland Heights, Ohio, United States
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Michael R. Kozlowski
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Ivy Samuels, None; Matthew Tarchick, None; Timothy Trobenter, None; Michael Kozlowski, None
  • Footnotes
    Support  VA Merit Award I01BX002754 (ISS), NEI/NIH P30 IP30EY025585, an Unrestricted Grant Award from Research to Prevent Blindness to the Dept of Ophthalmology, Cole Eye Institute (RPB1508DM), and a Foundation Fighting Blindness Center Grant to the Cole Eye Institute (CCMM08120584CCF)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5361. doi:
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    • Get Citation

      Ivy S Samuels, Matthew Tarchick, Timothy D. Trobenter, Michael R. Kozlowski; Systemic reduction of GLUT1 prevents hallmarks of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5361.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Clinical trials indicate that the severity of diabetic retinopathy (DR) varies with systemic blood glucose: inadequate glycemic control exacerbates retinopathy, while normalization of glucose levels delays its progression. Importantly, elevated blood glucose has a strong negative correlation with measures of EOG and ERG component amplitudes. These data implicate elevations in glucose as an important factor in early retina/RPE dysfunction as well as DR development, progression and severity. Our goal was to determine if reducing glucose within the retina decreased the incidence and severity of hallmarks of DR.

Methods : The facilitative glucose transporter, Glut1, is the principal means by which the retina obtains glucose. Glucose transport from the choroid into the RPE via Glut1 is induced by elevations in extracellular glucose levels. Loss of one functional allele of GLUT1 decreases the rate of glucose transport from the blood to the cerebrospinal fluid. In order to reduce glucose in the retina, we utilized wild-type (WT, Glut1+/+) and Glut1+/- mice. Both strains of mice were injected with streptozotocin and analyzed at 2 and 4 wks of diabetes. Glut1 expression in the RPE and retina and retinal structure were compared by immunohistochemistry, western blot and semi-thin plastic sectioning. Retinal and RPE function was assessed by dark-adapted and light-adapted strobe flash and dc-ERG. Oxidative stress and inflammation were measured by dihydroethidium staining and qPCR of inflammatory molecules.

Results : Glut1 levels were elevated in the RPE and retina of diabetic WT mice, specifically at the plasma membrane, while diabetic Glut1+/- mice exhibited a less robust increase in Glut1 levels. The amplitude of a-, b- and c-waves of diabetic WT mice were significantly lower than in diabetic GLUT1+/- mice at both 2 and 4 wks. Similarly, levels of oxidative stress and inflammatory markers were greater in WT diabetic animals as compared to GLUT1+/- mice. However, up to 4 wks of diabetes, no changes in retinal structure were observed in WT or Glut1+/- mice.

Conclusions : The reduction of Glut1 in diabetic mice significantly dampened the severity of defects in retinal function and presence of oxidative stress and inflammation. This data supports the hypothesis that hyperglycemia induces the earliest defects in retinal and RPE cell function associated with DR, and that these defects can be ameliorated by modulating glucose transport.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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