Prophylactic Medical Treatment of Diabetic Retinopathy

Tanaka

Ota

et al. 2014

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Purpose. To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats. Methods. The animals were divided into six groups, normal Sprague-Dawley rats (n = 8), untreated SDT rats (n = 9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day, n = 7, 8, and 6, resp.), and epalrestat-treated SDT rats (100 mg/kg/day, n = 7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured. Results. The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP. Conclusion. Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas.

Section: Introductionsupporting

confidence: 79%

Effect of Ranirestat, a New Aldose Reductase Inhibitor, on Diabetic Retinopathy in SDT Rats

Tanaka

Ota

et al. 2014

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“…Therefore, although DR in SDT rat mimics retinopathy in humans, to be precise it differs from that in humans. We reported accumulation of vascular endothelial growth factor (VEGF) and extensive fluorescein leakage around the optic nerve disc in the retinas of SDT rats [ 12 ], and we believe that the thickening in SDT rats is due to increasing retinal vascular permeability. Therefore, although typical NPDR in this experiment was not observed, we evaluated earlier DR as diabetic retinal edema in this experiment.…”

Section: Discussionmentioning

confidence: 99%

“…These findings suggested that a long duration of high blood glucose may affect the choroidal structure in SDT rats, but further transmission electron microscopy examinations are needed. We reported accumulation of VEGF and extensive fluorescein leakage around the optic nerve disc in the retinas of SDT rats [ 12 ]. Therefore, we suppose that the retinal edema results from increasing vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

Diabetic Retinal and Choroidal Edema in SDT Rats

Tanaka

Shimmura

et al. 2016

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We evaluated the features of diabetic retinal and choroidal edema in Spontaneously Diabetic Torii (SDT) rats. We measured the retinal and choroidal thicknesses in normal Sprague-Dawley (SD) rats (n = 9) and SDT rats (n = 8). The eyes were enucleated 40 weeks later after they were diagnosed with diabetes, and 4-micron sections were cut for conventional histopathologic studies. The mean retinal and choroidal thicknesses were significantly thicker in the SDT rats than in the normal SD rats. The choroidal thickness was correlated strongly with the retinal thickness in both rat models. Diabetic retinopathy (DR) and diabetic choroidopathy appeared as edema in the SDT rats. The retinal thickness was correlated strongly with the choroidal thickness in the SDT rats, which is an ideal animal model of both DR and choroidopathy.

“…Using this unique rat model, we tested the effect of ranirestat, a new ARI, on DR in SDT rats in a previous study. Ranirestat prevented development of proliferative DR in SDT rats [17]. We then conducted the current experiment to evaluate the effect of ranirestat on cataracts and DN in SDT rats and to compare the effect of the commercially available ARI epalrestat.…”

Section: Discussionmentioning

confidence: 99%

“…However, our previous study showed a strong preventative effect of an ARI, fidarestat, on the development of DR in spontaneously diabetic Torii (SDT) rats [16]. We recently confirmed that a newly developed ARI, ranirestat, is even more effective in preventing development of DR in SDT rats [17]. In the current study, we evaluated the effect of ranirestat on cataract and DN in SDT rats compared with the commercially available epalrestat.…”

Section: Introductionmentioning

confidence: 93%

Effects of Long-Term Treatment with Ranirestat, a Potent Aldose Reductase Inhibitor, on Diabetic Cataract and Neuropathy in Spontaneously Diabetic Torii Rats

Ota

Kakehashi

et al. 2013

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We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0–6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P < 0.01). Ranirestat significantly (P < 0.01) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently (P < 0.01). Epalrestat also reversed the prevented MNCV decrease (P < 0.05). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, (P < 0.05, <0.01, and <0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only.