Retinal dysfunction in diabetic Ren-2 rats is ameliorated by treatment with valsartan but not atenolol

Joanna Phipps, Jennifer Wilkinson-Berka, Erica Lucy Fletcher

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Abstract

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 beta1-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.
Original languageEnglish
Pages (from-to)927 - 934
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number2
Publication statusPublished - 2007

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