Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy

Erich Lieth, Alistair J. Barber, Baiyang Xu, Chelsea Dice, Michael J. Ratz, Diana Tanase, John M. Strother

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Abstract

The early pathophysiology of diabetic retinopathy and the involvement of neural and vascular malfunction are poorly understood. Glial cells provide structural and metabolic support for retinal neurons and blood vessels, and the cells become reactive in certain injury states. We therefore used the streptozotocin rat model of short-term diabetic retinopathy to study glial reactivity and other glial functions in the retina in the first months after onset of diabetes. With a two-site enzyme-linked immunosorbent assay, we measured the expression of the intermediate filament glial fibrillary acidic protein (GFAP). After 1 month, GFAP was largely unchanged, but within 3 months of the beginning of diabetes, it was markedly induced, by fivefold (P < 0.04). Immunohistochemical staining showed that the GFAP induction occurred both in astrocytes and in Muller cells. Consistent with a glial cell malfunction, the ability of retinas to convert glutamate into glutamine, assayed chromatographically with an isotopic method, was reduced in diabetic rats to 65% of controls (P <0.01). Furthermore, retinal glutamate, as determined by luminometry, increased by 1.6-fold (P < 0.04) after 3 months of diabetes. Taken together, these findings indicate that glial reactivity and altered glial glutamate metabolism are early pathogenic events that may lead to elevated retinal glutamate during diabetes. These data are the first demonstration of a specific defect in glial cell metabolism in the retina during diabetes. These findings suggest a novel understanding of the mechanism of neural degeneration in the retina during diabetes, involving early and possibly persistent glutamate excitotoxicity.

Original languageEnglish (US)
Pages (from-to)815-820
Number of pages6
JournalDiabetes
Volume47
Issue number5
DOIs
StatePublished - May 14 1998

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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