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Comparison of three strains of diabetic rats with respect to the rate at which retinopathy and tactile allodynia develop.

Kern TS, Miller CM, Tang J, Du Y, Ball SL, Berti-Matera L - Mol. Vis. (2010)

Bottom Line: Cyclooxygenase 2 (COX2) was significantly elevated in the Sprague Dawley and Wistar strains.All strains tended to show diabetes-induced impairment of dark-adapted b-wave amplitude, but only Sprague Dawley and Lewis strains had a significant reduction in latency.All strains showed significant tactile allodynia in peripheral nerves.

View Article: PubMed Central - PubMed

Affiliation: Case Western Reserve University, Center for Diabetes Research, Cleveland, OH 44106, USA. tsk@case.edu

ABSTRACT

Purpose: We compared three rat strains to determine if different strains develop early-stage diabetic retinopathy or sensory neuropathy at different rates.

Methods: Sprague Dawley, Lewis, and Wistar rats were made diabetic with streptozotocin. Diabetic and nondiabetic animals had retinal vascular pathology measured at eight months of diabetes. The number of cells in the retinal ganglion cell layer (GCL), retinal function (using electroretinography [ERG]), and retinal levels of inducible nitric oxide synthase (iNOS), cyclooxygenase2 (COX2), and vascular endothelial growth factor (VEGF) were measured at four months of diabetes. Tactile allodynia was assessed in hind paws at two months of diabetes.

Results: Diabetes of eight months' duration resulted in a significant increase in retinal degenerate capillaries and pericyte ghosts in Lewis and Wistar rats, but not in Sprague Dawley rats. A significant loss of cells in the GCL occurred only in diabetic Lewis rats, whereas Wistar and Sprague Dawley rats showed little change. Diabetes-induced iNOS and VEGF were statistically significant in all strains. Cyclooxygenase 2 (COX2) was significantly elevated in the Sprague Dawley and Wistar strains. Lewis rats showed a similar trend, however, the results were not statistically significant. All strains tended to show diabetes-induced impairment of dark-adapted b-wave amplitude, but only Sprague Dawley and Lewis strains had a significant reduction in latency. All strains showed significant tactile allodynia in peripheral nerves.

Conclusions: At the durations studied, Lewis rats showed accelerated loss of both retinal capillaries and ganglion cells in diabetes, whereas diabetic Wistar rats showed degeneration of the capillaries without significant neurodegeneration, and Sprague Dawley rats showed neither lesion. Identification of strains that develop retinal lesions at different rates should be of value in investigating the pathogenesis of retinopathy.

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Diabetes of four months’ duration caused a significant decrease in the number of cells in the GCL of the retina in Lewis rats, but not Wistar rats. Sprague Dawley diabetic rats tended to show fewer cells in the GCL compared to nondiabetic controls, but the results were not statistically significant. All groups contained more than eight animals. Mean±SEM.
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f2: Diabetes of four months’ duration caused a significant decrease in the number of cells in the GCL of the retina in Lewis rats, but not Wistar rats. Sprague Dawley diabetic rats tended to show fewer cells in the GCL compared to nondiabetic controls, but the results were not statistically significant. All groups contained more than eight animals. Mean±SEM.

Mentions: Nonvascular cells of the retina have also been reported to degenerate in diabetes. At four months of diabetes, the number of cells in the GCL was counted in retinal cross-sections through the optic nerve. As summarized in Figure 2, only Lewis rats showed a significant reduction in the number of cells in the GCL compared to nondiabetic controls (p<0.05). The statistical significance of this reduction in the Lewis strain was due to changes in the posterior retina only; none of the strains showed a statistically significant reduction in numbers of cells in the GCL in the mid-retina region (not shown). To determine if strain differences in the rate of ganglion cell loss influenced retinal function, we also measured retinal function via light- and dark-adapted ERG in diabetic and nondiabetic animals of all three strains. Lewis rats showed greater changes in amplitude in response to light than did other strains. Diabetes of four months’ duration reduced the latency of rod-mediated b-waves in Sprague Dawley and Lewis strains (p<0.05; Figure 3). Amplitudes of the dark-adapted b-waves tended to be subnormal in diabetics of all three strains, but the results were not statistically significant. Comparisons at individual light intensities (by t-test) indicated that rod-mediated b-wave amplitudes in diabetics were significantly different from normal only at higher intensities for all three strains. The only cone-mediated b-wave process that was significantly altered by diabetes was amplitude, only at the highest intensity, in Sprague Dawley and Lewis strains (not shown).


Comparison of three strains of diabetic rats with respect to the rate at which retinopathy and tactile allodynia develop.

Kern TS, Miller CM, Tang J, Du Y, Ball SL, Berti-Matera L - Mol. Vis. (2010)

Diabetes of four months’ duration caused a significant decrease in the number of cells in the GCL of the retina in Lewis rats, but not Wistar rats. Sprague Dawley diabetic rats tended to show fewer cells in the GCL compared to nondiabetic controls, but the results were not statistically significant. All groups contained more than eight animals. Mean±SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927372&req=5

f2: Diabetes of four months’ duration caused a significant decrease in the number of cells in the GCL of the retina in Lewis rats, but not Wistar rats. Sprague Dawley diabetic rats tended to show fewer cells in the GCL compared to nondiabetic controls, but the results were not statistically significant. All groups contained more than eight animals. Mean±SEM.
Mentions: Nonvascular cells of the retina have also been reported to degenerate in diabetes. At four months of diabetes, the number of cells in the GCL was counted in retinal cross-sections through the optic nerve. As summarized in Figure 2, only Lewis rats showed a significant reduction in the number of cells in the GCL compared to nondiabetic controls (p<0.05). The statistical significance of this reduction in the Lewis strain was due to changes in the posterior retina only; none of the strains showed a statistically significant reduction in numbers of cells in the GCL in the mid-retina region (not shown). To determine if strain differences in the rate of ganglion cell loss influenced retinal function, we also measured retinal function via light- and dark-adapted ERG in diabetic and nondiabetic animals of all three strains. Lewis rats showed greater changes in amplitude in response to light than did other strains. Diabetes of four months’ duration reduced the latency of rod-mediated b-waves in Sprague Dawley and Lewis strains (p<0.05; Figure 3). Amplitudes of the dark-adapted b-waves tended to be subnormal in diabetics of all three strains, but the results were not statistically significant. Comparisons at individual light intensities (by t-test) indicated that rod-mediated b-wave amplitudes in diabetics were significantly different from normal only at higher intensities for all three strains. The only cone-mediated b-wave process that was significantly altered by diabetes was amplitude, only at the highest intensity, in Sprague Dawley and Lewis strains (not shown).

Bottom Line: Cyclooxygenase 2 (COX2) was significantly elevated in the Sprague Dawley and Wistar strains.All strains tended to show diabetes-induced impairment of dark-adapted b-wave amplitude, but only Sprague Dawley and Lewis strains had a significant reduction in latency.All strains showed significant tactile allodynia in peripheral nerves.

View Article: PubMed Central - PubMed

Affiliation: Case Western Reserve University, Center for Diabetes Research, Cleveland, OH 44106, USA. tsk@case.edu

ABSTRACT

Purpose: We compared three rat strains to determine if different strains develop early-stage diabetic retinopathy or sensory neuropathy at different rates.

Methods: Sprague Dawley, Lewis, and Wistar rats were made diabetic with streptozotocin. Diabetic and nondiabetic animals had retinal vascular pathology measured at eight months of diabetes. The number of cells in the retinal ganglion cell layer (GCL), retinal function (using electroretinography [ERG]), and retinal levels of inducible nitric oxide synthase (iNOS), cyclooxygenase2 (COX2), and vascular endothelial growth factor (VEGF) were measured at four months of diabetes. Tactile allodynia was assessed in hind paws at two months of diabetes.

Results: Diabetes of eight months' duration resulted in a significant increase in retinal degenerate capillaries and pericyte ghosts in Lewis and Wistar rats, but not in Sprague Dawley rats. A significant loss of cells in the GCL occurred only in diabetic Lewis rats, whereas Wistar and Sprague Dawley rats showed little change. Diabetes-induced iNOS and VEGF were statistically significant in all strains. Cyclooxygenase 2 (COX2) was significantly elevated in the Sprague Dawley and Wistar strains. Lewis rats showed a similar trend, however, the results were not statistically significant. All strains tended to show diabetes-induced impairment of dark-adapted b-wave amplitude, but only Sprague Dawley and Lewis strains had a significant reduction in latency. All strains showed significant tactile allodynia in peripheral nerves.

Conclusions: At the durations studied, Lewis rats showed accelerated loss of both retinal capillaries and ganglion cells in diabetes, whereas diabetic Wistar rats showed degeneration of the capillaries without significant neurodegeneration, and Sprague Dawley rats showed neither lesion. Identification of strains that develop retinal lesions at different rates should be of value in investigating the pathogenesis of retinopathy.

Show MeSH
Related in: MedlinePlus