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K. Kozaki, A. J. Vingrys, B. V. Bui; Time Course of Ganglion Cell Dysfunction in Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):167.
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We consider the time course of retinal dysfunction in diabetic animals. In particular we compare the effect of diabetes on electroretinogram (ERG) components arising from the outer (photoreceptors, bipolar cells) and inner retina (ganglion cells).
ERG responses were assessed (-6.08 to 1.92 log cd.s.m-2) in anaesthetized (60 : 5 mg/kg ketamine:xylazine) dark-adapted (>12 hours)adult Sprague-Dawley rats at 4, 8 and 10 weeks following diabetogenesis (n = 12, 50 mg/kg streptozotocin). Diabetes was induced at 6 weeks of age and STZ treated animals were given 2 units of insulin each day. STZ retinal function was compared with control (n = 12, citrate buffer) in terms of photoreceptor (a-wave), bipolar (b-wave), amacrine (oscillatory potentials, OPs) and ganglion cell (positive scotopic threshold response, STR) components. Data are expressed relative to mean control amplitudes. Two-way repeated measure ANOVA was employed to compare treatment effect across time, with Bonferroni post-hoc tests used at selected time points.
Photoreceptoral (a-wave, at 10 weeks +3 ± 7%) and bipolar cell (b-wave at 10 weeks -8 ± 2%) responses were not significantly reduced by STZ treatment throughout the experiment. The OPs were not affected at 4 weeks (-10 ± 9%), but were significantly reduced at 8 (-25 ± 7%, P < 0.01) and 10 weeks (-22 ± 11%). The most severely affected component was the ganglion cell dominated positive STR, which was reduced by -43 ± 9% at 4 weeks, -54 ± 12% and progressed to -53 ± 10% by 10 weeks. The negative STR was initially increased at 4 weeks (+31 ± 7%) and 8 weeks (+23 ± 12%) by STZ treatment. However, by 10 weeks the nSTR had returned to normal levels (+11 ± 10%). This paradoxical nSTR increase reflects the relatively early loss of the pSTR.
The positive component of the STR is the most sensitive component to diabetes and in rats is known to be dominated by ganglion cell activity. Ganglion cell dysfunction in STZ diabetes is detectable 4 weeks following diabetogenesis, before other ERG components are affected. This outcome suggests that ganglion cells are affected early in diabetes.
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