Diabetes-induced impairment in visual function in mice: Contributions of p38 MAPK, RAGE, leukocytes, and aldose reductase

Chieh Allen Lee, Guangyuan Li, Mansi D. Patel, J. Mark Petrash, Beth Ann Benetz, Alex Veenstra, Jaume Amengual, Johannes von Lintig, Christopher J. Burant, Johnny Tang, Timothy S. Kern

Research output: Contribution to journalArticlepeer-review


PURPOSE. Visual function is impaired in diabetes, but molecular causes of this dysfunction are not clear. We assessed effects of diabetes on visual psychophysics in mice, and tested the effect of therapeutic approaches reported previously to inhibit vascular lesions of the retinopathy. METHODS. We used the optokinetic test to assess contrast sensitivity and spatial frequency threshold in diabetic C57Bl/6J mice and age-matched nondiabetic controls between 2 and 10 months of diabetes. Contributions of p38 MAP kinase (MAPK), receptor for advanced glycation end products (RAGE), leukocytes, and aldose reductase (AR) to the defect in contrast sensitivity were investigated. Cataract, a potential contributor to reductions in vision, was scored. RESULTS. Diabetes of 2 months' duration impaired contrast sensitivity and spatial frequency threshold in mice. The defect in contrast sensitivity persisted for at least 10 months, and cataract did not account for this impairment. Diabetic mice deficient in AR were protected significantly from development of the diabetes-induced defects in contrast sensitivity and spatial frequency threshold. In contrast, pharmacologic inhibition of p38 MAPK or RAGE, or deletion of inducible nitrous oxide synthase (iNOS) from bone marrow-derived cells did not protect the visual function in diabetes. CONCLUSIONS. Diabetes reduces spatial frequency threshold and contrast sensitivity in mice, and the mechanism leading to development of these defects involves AR. The mechanism by which AR contributes to the diabetes-induced defect in visual function can be probed by identifying which molecular abnormalities are corrected by AR deletion, but not other therapies that do not correct the defect in visual function.

Original languageEnglish (US)
Pages (from-to)2904-2910
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Issue number5
StatePublished - Aug 6 2013
Externally publishedYes


  • Contrast senstivity
  • Diabetic retinopathy
  • Spatial frequency threshold

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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