Abstract
Purpose: :
To study the effects of sustained hyperglycemia on function, neurotransmitter distribution and D–aspartate uptake in retina using an established animal model of type 1 diabetes mellitus.
Methods: :
Non–fasted male Sprague–Dawley rats received either a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg body weight) or an equal volume of citrate buffer (pH 4.5) as a vehicle control. Blood glucose was determined biweekly using a commercial glucometer. At 0, 3, 6, 9, and 12 weeks, rats were dark–adapted x 2h, anesthetized, pupils fully dilated and electroretinogram (ERG) responses were recorded. At 12 weeks, retinal neurotransmitter distribution and D–aspartate uptake were determined by immunogold immuno–histochemistry with silver intensification.
Results: :
Rats treated with a single injection of STZ developed elevated levels of blood glucose (528.7 + 47.4 mg%, n=3, p<0.0001), compared to vehicle–treated control (100.8 + 6.7 mg%, n=4), that were sustained for the duration of the study. At 6, 9, and 12 weeks following STZ–treatment, ERG oscillatory potential amplitudes were found to be significantly (p< 0.05) reduced in STZ treated rats compared to vehicle–treated controls. Changes in ERG a– and b–waves, retinal morphology, and the distribution of the retinal neurotransmitters glutamate and glutamine were not significantly affected by sustained hyperglycemia. D–Aspartate uptake by cells of the retinal inner nuclear layer was significantly increased in STZ–treated rats (13.6 + 1.96 / 1000µm2, p<0.01) compared to vehicle–treated controls (5.8 + 0.39 / 1000 µm2).
Conclusions: :
Sustained hyperglycemic insult to Sprague–Dawley male rats elicited early visual deficits as quantitated by changes of ERG oscillatory potentials. Altered retinal function was not associated with changes in retinal morphology, glutamate and glutamine neurotransmitter distribution. Increased D–aspartate transport by cells of the inner nuclear layer may serve a compensatory protective role in the early phase of diabetic retinopathy.
Keywords: diabetic retinopathy • immunohistochemistry • neurotransmitters/neurotransmitter systems