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D.J. Ramsey, H. Qian; Characterization of the Electroretinogram in Female Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3093.
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The prevalence of diabetes is largely equal among men and women. However, most experimental investigations have focused on male animals to study the effects of diabetes on visual function. This is particularly striking considering male rats have a different physiological response to STZ–induced diabetes when compared to their female counterparts. The present study examines the effects of diabetes on the flash electroretinogram (ERG) in STZ–induced diabetic female rats. In particular, we focus on the oscillatory potentials (OPs) as a benchmark for neurosensory defects in early diabetes.
Female Long Evans rats (80±3 days old; 218±6g) received streptozotocin (STZ) dissolved in 0.9% Na citrate buffer (i.v. 60 mg/kg; pH 4.5). Diabetes was established by demonstrating a BGL >350 mg/dl. The ERG was recorded at 12 weeks using a UTAS–E 3000 ERG system (LKC Technologies) following dark–adaptation overnight. A band pass digital filter (40–200 Hz) was used to isolate the OPs. The expression of GABA and GFAP was assessed immunohistochemically and analyzed on a confocal microscope.
For the duration of the study, diabetic rats (n=7) demonstrated no significant weight change, whereas control animals (n=8) demonstrated linear weight gain. At 12 weeks, no statistical different was observed in the sensitivity or amplitude of the a– or b–waves under diabetic conditions. Diabetic animals showed a significant decline in the implicit time of the b–wave at bright flash intensities (p<0.05). A small, but significant delay in the implicit time of the a–wave was also appreciated (p<0.01). In addition, diabetes caused a significant decline in the first OP (p<0.001), but increased the magnitude of later OPs (OP4 and OP5; p<0.01). The time–to–peak of the OPs was also lengthened by ∼5ms in diabetic animals (P<0.01). Significantly enhanced immunofluoresce for both GFAP and GABA was detected in the retina of diabetic animals compared to controls.
Like their male counterparts, the retina of female diabetic rats had an up–regulation of GFAP and an accumulation of GABA in retinal Müller cells, as well as a reduction in the earlier OPs of the ERG. These results provide evidence for an alteration in the GABA signaling pathway in the diabetic retina. We find no significant reduction in the b–wave of the ERG at 12 weeks, in contrast to other studies that have used male rats. It is possible that this difference may be a gender specific effect of streptozotocin–induced diabetes in the rat.
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