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Kasumi Kikuchi, Kousuke Noda, Miyuki Murata, Atsuhiro Kanda, Satoru Kase, Yasushi Kageyama, Masami Shinohara, Tomohiko Sasase, Susumu Ishida; Involvement of polyol pathway and oxidative stress in cataract formation in Spontaneously Diabetic Torii fatty rats.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1019.
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© ARVO (1962-2015); The Authors (2016-present)
Spontaneously Diabetic Torii (SDT) fatty rat is a novel animal model of obese type 2 diabetes and they develop diabetic cataract. It is elucidated that excessive glucose enters to the polyol pathway and is reduced to sorbitol by aldose reductase, leading to osmotic stress in lens epithelial cells under hyperglycemic condition. Thereafter, sorbitol is oxidized to fructose by sorbitol dehydrogenase, which increases oxidative stress via consumption of NAD+. Previously, we reported glucose elevation and glutathione depletion in the lens in SDT fatty rat. In this study, we sought to further investigate the involvements of polyol pathway and oxidative stress in cataract formation in SDT fatty rats.
Male SDT fatty rats and age-matched Sprague-Dawley (SD) rats (CLEA Japan, Inc.) were used. At 5, 8, 12, 16 weeks of age, the rats were euthanized and the eyes were enucleated. The levels of sorbitol, fructose and4-hydroxynonenal (HNE) were measured in the lens samples.
Lens sorbitol level increased in SDT fatty rats at 8, 12 and 16 weeks of age (8w, 21.7±0.9nmol/mg; 12w, 26.2±1.7nmol/mg; 16w, 9.3±0.7nmol/mg) and sorbitol was not detected in lens of SD rats for any ages. SDT fatty ratsshowed 3.5-fold and 1.6-fold increases in lens fructose levelat 8 and 16 weeks of age, respectively, in comparison with the control group (p<0.01). In addition, lens 4-HNE levels increased 1.7- and 1.4-fold in SDT fatty ratsat 12 and 16 weeks of age, respectively,compared to the control group.(p<0.01).
The current study indicated that glucose flux into the polyol pathway causes the accumulation of sorbitol and fructose, both of which increase oxidative stress, in the lens of SDT fatty rat.
This is a 2020 ARVO Annual Meeting abstract.
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