June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Deletion of GLUT1 in mouse lens epithelium leads to cataract formation
Author Affiliations & Notes
  • Aditi Swarup
    Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Arturo Bravo-Nuevo
    Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Jamie Soto
    Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, United States
    Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
  • E. Dale Abel
    Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, United States
    Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
  • Brent A Bell
    Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Neal Peachey
    Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
    Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, United States
  • Paul G FitzGerald
    Cell Biology and Human Anatomy, U.C. Davis, Davis, California, United States
  • Nancy J Philp
    Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Aditi Swarup, None; Arturo Bravo-Nuevo, None; Jamie Soto, None; E. Dale Abel, None; Brent Bell, None; Neal Peachey, None; Paul FitzGerald, None; Nancy Philp, None
  • Footnotes
    Support  NIH (R01 EY012042, P30 EY025585), VA (I01 BX002340), Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2038. doi:
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      Aditi Swarup, Arturo Bravo-Nuevo, Jamie Soto, E. Dale Abel, Brent A Bell, Neal Peachey, Paul G FitzGerald, Nancy J Philp; Deletion of GLUT1 in mouse lens epithelium leads to cataract formation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2038.

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

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Abstract

Purpose : The ocular lens is avascular and depends on glycolysis for energy production. GLUT1, a member of the SLC2 family of glucose transporters, is polarized to the basolateral membrane of the lens epithelium (LE) suggesting it facilitates the uptake of glucose from the aqueous humor. In these studies we examined whether GLUT1 plays a critical role of maintaining metabolic homeostasis in the lens by studying effects of postnatal deletion of GLUT1 in the lens.

Methods : In situ hybridyzation and immunolabeling were used to determine the expression and subcellular localization of GLUT1 in the lens. GLUT1 was knocked out of LE by crossing transgenic mice expressing Cre under control of the GFAP promoter with Glut1Flox/Flox mice to generate Tg-GFAP-cre:Glut1Flox/Flox mice. It has been previously reported that GFAP is present in the LE. All mice were of C57BL/6 strain. Because GFAP is also expressed in Müller glial cells (MGCs), we crossed the Glut1Flox/Flox line with PDGFR-Cre animals, as this transgene targets Cre expression to MGCs but not the lens. Optical Coherence Tomography (OCT) was used to monitor the cataract formation over the course of 6 months. ATP and lactate were measured using commercially available kits. Fluorescently labeled glucose (2-NBDG) was used to check glucose uptake by the lens.

Results : There was a progressive loss of GLUT1 expression in the Tg-GFAP-cre:Glut1Flox/Flox lens as a function of age. Opacity in the lens was first detected by visual observation and by OCT changes at 2.8 months and cataract formation was temporally correlated with GLUT1 deficiency. In the Tg-GFAP-cre:Glut1Flox/Flox lens, secondary fiber cells failed to elongate and migrate properly and nuclei were not cleared from these cells. With age, the number of disorganized fiber cells increased and in some instances the capsule was disrupted. These changes were not noted in the lenses of Tg-PDGFR-cre:Glut1Flox/Flox mice. ATP and lactate levels were significantly lower in lenses from 3.6 month old Tg-GFAP-cre:Glut1Flox/Flox mice as compared to their age-matched controls. Also, LE in these mice showed diminished 2-NBDG uptake.

Conclusions : Glucose transport into the LE is required to maintain lens transparency. In the mouse, this glucose transport is achieved via the GLUT1 transporter. Dysregulation of GLUT1 could play a role in hypoglycemia-induced and inherited cataract conditions.

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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