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Neuroscience
Hypoglycemia leads to age-related loss of vision
( C57BL/6J mice | cell death | glucagon receptor gene | retinal function | visual acuity )
Y. Umino *, D. Everhart *, E. Solessio *, K. Cusato *, J. C. Pan *, T. H. Nguyen *, E. T. Brown *, R. Hafler *, B. A. Frio *, B. E. Knox *, G. A. Engbretson *, M. Haeri *, L. Cui , A. S. Glenn , M. J. Charron , and R. B. Barlow *
*Center for Vision Research, Department of Ophthalmology, State University of New York Upstate Medical University, Syracuse, NY 13210; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461; and Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244
Edited by John E. Dowling, Harvard University, Cambridge, MA, and approved November 1, 2006 (received for review May 31, 2006)
The retina is among the most metabolically active tissues in the body, requiring a constant supply of blood glucose to sustain function. We assessed the impact of low blood glucose on the vision of C57BL/6J mice rendered hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr. Metabolic stress from moderate hypoglycemia led to late-onset loss of retinal function in Gcgr-/- mice, loss of visual acuity, and eventual death of retinal cells. Retinal function measured by the electroretinogram b-wave threshold declined >100-fold from age 9 to 13 months, whereas decreases in photoreceptor function measured by the ERG a-wave were delayed by 3 months. At 10 months of age Gcgr-/- mice began to lose visual acuity and exhibit changes in retinal anatomy, including an increase in cell death that was initially more pronounced in the inner retina. Decreases in retinal function and visual acuity correlated directly with the degree of hypoglycemia. This work demonstrates a metabolic-stress-induced loss of vision in mammals, which has not been described previously. Linkage between low blood glucose and loss of vision in mice may highlight the importance for glycemic control in diabetics and retinal diseases related to metabolic stress as macular degeneration.
Author contributions: Y.U., D.E., E.S., B.E.K., and R.B.B. designed research; Y.U., D.E., E.S., K.C., J.C.P., T.H.N., E.T.B., R.H., B.A.F., G.A.E., and M.H. performed research; L.C., A.S.G., and M.J.C. contributed new reagents/analytic tools; Y.U., D.E., E.S., J.C.P., T.H.N., and R.B.B. analyzed data; and Y.U., D.E., K.C., and R.B.B. wrote the paper.
The authors declare no conflict of interest.
Freely available online through the PNAS open access option.
To whom correspondence should be addressed at: Center for Vision Research, Department of Ophthalmology, 3258 Weiskotten Hall, 750 East Adams Street, SUNY Upstate Medical University, Syracuse, NY 13210.
R. B. Barlow, E-mail: barlowr@upstate.edu
www.pnas.org/cgi/doi/10.1073/pnas.0604478104
http://www.pnas.org/cgi/content/abstract/0604478104v1?ct=ct |
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