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Joanna A. Phipps, Jennifer L. Wilkinson-Berka, Erica L. Fletcher; Retinal Dysfunction in Diabetic Ren-2 Rats Is Ameliorated by Treatment with Valsartan but Not Atenolol. Invest. Ophthalmol. Vis. Sci. 2007;48(2):927-934. doi: https://doi.org/10.1167/iovs.06-0892.
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purpose. To determine whether diabetes leads to retinal neuronal dysfunction in hypertensive transgenic (mRen-2)27 rats (Ren-2), and whether the effect can be prevented by treatment of hypertension with either the angiotensin-1 receptor blocker (AT1-RB) valsartan or the β1-adrenergic receptor antagonist atenolol.
methods. Six-week-old Ren-2 rats were made diabetic (streptozotocin 55 mg/kg; n = 34) or remained nondiabetic (0.1 M citrate buffer; n = 43) and studied for 20 weeks. A subset of animals received valsartan (4 mg/kg per day) or atenolol (30 mg/kg per day) by gavage. Sprague-Dawley (SD) rats served as normotensive controls for blood pressure (BP). We evaluated retinal function in all groups with a paired-flash electroretinogram over high light intensities (0.5–2.0 log cd-s · m−2), to isolate rod and cone responses.
results. A reduction in amplitude of all electroretinogram components (PIII, PII, OPs, cone PII) was found in nondiabetic Ren-2 compared with nondiabetic SD rats. A further reduction was observed in diabetic Ren-2 rats. Treatment of both nondiabetic and diabetic Ren-2 rats with valsartan or atenolol reduced BP to within normal limits. This reduction produced some improvement in function in treated nondiabetic Ren-2 rats. However, in treated diabetic Ren-2 rats, retinal dysfunction was ameliorated by valsartan but not by atenolol, with a significant improvement (P < 0.05) observed in all components of the electroretinogram, with the exception of the OPs.
conclusions. These findings suggest that hypertension induces retinal dysfunction that is exacerbated with diabetes and ameliorated by treatment with an AT1-RB, and not just by normalizing BP. These data provide further evidence for the importance of the renin-angiotensin system in development of diabetic complications.
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