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Updated: Sep 28, 2026
Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
[Ameliorative effects on retinal disorder in diabetic SHRSP (stroke-prone spontaneously hypertensive rat)]
Yasutaka Nagisa1, Asae Shintani, Shizue Nakagawa
1Pharmacology Research Laboratories II, Pharmaceutical Research Division, Takeda Chemical Industries Ltd.
Abstract:
The results of the EUCLID highlighted the importance of the renin-angiotensin system in the pathogenesis of diabetic retinopathy. We aimed to evaluate the effectiveness of candesartan cilexetil(TCV-116), a potent angiotensin II receptor antagonist, in ameliorating retinal disorders in stroke-prone spontaneously hypertensive rats(SHRSP) with storeptozotocin(STZ)-induced diabetes. Retinal VEGF mRNA expression was significantly higher and the latencies of oscillatory potentials were significantly elongated in STZ-treated SHRSP compared with a non-treated SHRSP group matched for age. Treatment with TCV-116(3 mg/kg) significantly diminished retinal VEGF mRNA expression and the latencies of oscillatory potentials, but had no effect on plasma glucose concentrations. These results suggest that TCV-116 is effective in preventing the development of diabetic retinopathy already in the early stages.
Insights
Candesartan cilexetil effectively prevents early diabetic retinopathy by reducing retinal VEGF mRNA and oscillatory potential latencies in diabetic rats. This angiotensin II receptor blocker shows promise for managing retinal disorders.
Area of Science:
- Ophthalmology
- Endocrinology
- Pharmacology
Context:
- Diabetic retinopathy is a significant complication of diabetes mellitus.
- The renin-angiotensin system plays a role in diabetic retinopathy pathogenesis.
- Stroke-prone spontaneously hypertensive rats (SHRSP) with streptozotocin (STZ)-induced diabetes serve as a model for diabetic complications.
Purpose:
- To evaluate the efficacy of candesartan cilexetil (TCV-116), an angiotensin II receptor antagonist, in ameliorating retinal disorders in a rat model of diabetes.
- To assess the impact of TCV-116 on retinal VEGF mRNA expression and oscillatory potential latencies.
Summary:
- STZ-treated SHRSP exhibited increased retinal VEGF mRNA expression and prolonged oscillatory potential latencies compared to non-diabetic controls.
- Treatment with TCV-116 (3 mg/kg) significantly reduced retinal VEGF mRNA and oscillatory potential latencies.
- TCV-116 did not affect plasma glucose concentrations, indicating a direct effect on retinal pathology.
Impact:
- Candesartan cilexetil demonstrates potential in preventing the early development of diabetic retinopathy.
- Targeting the renin-angiotensin system may be a viable therapeutic strategy for diabetic eye disease.
- These findings support the investigation of angiotensin II receptor antagonists for diabetic retinopathy management.
