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M. K. Kim, R. Amarnath, D. E. Olson, T. Q. Duong, P. M. Thule, M. T. Pardue; Low Intensity Stimuli Enhance Sensitivity of Scotopic Electroretinogram to Detect Early Neuronal Changes in STZ-Induced Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2212.
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The diagnosis of clinical diabetic retinopathy (DR) hinges on the discovery of vascular abnormalities. While, recent studies suggest that neuronal defects predate vasculature changes, how early neural defects emerge is unclear. We used dark-adapted electroretinograms (ERG) to non-invasively probe rod and rod/cone pathways in diabetic rat retinas to determine the onset of retinal dysfunction.
Dark-adapted baseline ERGs were obtained from 1.5 months old Sprague-Dawley rats. One subset served as untreated controls (n=6), while the other (n=8) was made diabetic by streptozotocin (STZ-DM) administration. Diabetes was confirmed by serially elevated blood glucose (>200 mg/dl) and monitored throughout the study. Rats were treated with low-doses of insulin to maintain weight and prevent diabetic ketoacidosis. At 5, 9, 14, and 21 weeks post-STZ injection, both groups of animals were dark adapted and scotopic ERGs performed in response to stimuli ranging from 3.9x10-4 to 137 cd sec/m2. The amplitude and latency of a-wave, b-wave, and oscillatory potentials (OP1, OP2, OP3, and OP4) were measured for representative dim (0.02 cd sec/m2) and bright (4.1 cd sec/m2) flash intensities.
In response to a dim flash, all four OP wavelets showed significantly delayed latencies in STZ-DM rats compared to controls which progressed over time (ANOVA, p < 0.001). In contrast, no differences in OP latencies were measured in response to a bright flash at any timepoint. Similarly, in response to dim flashes both a- and b-wave amplitudes were decreased in STZ-DM rats (5 to 14wks post-diabetes) and a-wave latencies were delayed. In response to bright flash, only small changes (p = 0.049) in b-wave amplitude and implicit time were measured at the 14week time point. No other changes were detected in response to bright flash stimuli for the other ERG waveform parameters.
Dim flash stimuli showed greater sensitivity than bright flash stimuli at detecting early changes in DR in the STZ-DM rat. As expected, OP latency had the greatest sensitivity to DR changes, suggesting alterations in the inner retinal function with DR. Since clinical ERG recordings typically only analyze OPs in responses to bright flash stimuli, these results indicate that OP responses to dim flash stimuli may offer a more sensitive, non-invasive method to detect early neuronal changes in DR.
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