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Akihiro Kakehashi, Fumihiko Toyoda, Hodaka Hodaka, Mina Kobayashi, Rina Takagi, Yoshiaki Tanaka, Machiko Shimmura, Hiroko Takano; Effect of tofogliflozin, a SGLT-2 inhibitor, on diabetic ocular complications in SDT rats. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5794.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effect of tofogliflozin (Kowa Pharmaceutical Co. Ltd., Tokyo, Japan), a sodium-glucose co-transporter (SGLT)-2 inhibitor, on diabetic ocular complications in spontaneously diabetic Torii (SDT) rats.
The rats were divided into three groups: 12 normal Sprague-Dawley (SD) rats, 11 untreated SDT rats, and 11 tofogliflozin-treated SDT rats. The tofogliflozin-treated rats were fed chow containing tofogliflozin 0.005%. Blood tests, biomicroscopic examinations of the cataracts, and histopathologic study of the eyes were done at 20 and 40 weeks after diabetes onset and in normal age-matched SD rats. The cataracts were classified biomicroscopically as minimal, mild, or severe. Retinopathy was evaluated based on the retinal thickness 500 microns from the optic disc.
At 20 and 40 weeks, respectively, the median blood glucose levels were 182 mg/dl (range, 172-205 mg/dl) and 160 mg/dl (range, 141-173 mg/dl) in normal SD rats, 785 mg/dl (range, 741-940 mg/dl) and 924 mg/dl (range, 888-1000 mg/dl) in untreated SDT rats, and 497 mg/dl (range, 368-625 mg/dl) and 617 mg/dl (range, 403-663 mg/dl) in tofogliflozin-treated rats. The median blood glucose level in the tofogliflozin-treated rats was significantly (p<0.05) lower than in the untreated SDT rats. Cataracts did not develop in the normal SD rats at any age. Severe cataracts developed 20 weeks after diabetes onset in all untreated SDT rats. However, cataract development in the tofogliflozin-treated rats was significantly less at 20 weeks (minimal 19 [86%] eyes, p<0.01; moderate 3 [14%] eyes, p<0.05; and severe no eyes, p<0.01) and at 40 weeks in six of the 11 rats examined (minimal eight [67%] eyes, p<0.01; moderate 4 [33%] eyes, p<0.01; and severe no eyes, p<0.01) compared with the untreated SDT rats. The median retinal thickness was 138.5 µm (range, 107-157 µm) in the tofogliflozin-treated rats and 157.5 µm (range, 128-190 µm) in the untreated rats 20 weeks after diabetes onset. Although the difference in the retinal thickness was significant (p<0.05) between those groups 20 weeks after diabetes onset, no significant difference was seen at 40 weeks.
Tofogliflozin prevented cataracts and retinopathy in SDT rats.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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