Hypoglycemia leads to age-related loss of vision

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, R. B. Barlow

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)19541-19545
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number51
DOIs
StatePublished - Dec 19 2006

Keywords

  • C57BL/6J mice
  • Cell death
  • Glucagon receptor gene
  • Retinal function
  • Visual acuity

ASJC Scopus subject areas

  • General

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    Umino, Y., Everhart, D., Solessio, E., Cusato, K., Pan, J. C., Nguyen, T. H., Brown, E. T., Hafler, R., Frio, B. A., Knox, B. E., Engbretson, G. A., Haeri, M., Cui, L., Glenn, A. S., Charron, M. J., & Barlow, R. B. (2006). Hypoglycemia leads to age-related loss of vision. Proceedings of the National Academy of Sciences of the United States of America, 103(51), 19541-19545. https://doi.org/10.1073/pnas.0604478104