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Wei Wang, Amy CY Lo; Study on the effect of lutein in an experimental model of diabetic retinopathy using the Ins2Akita mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):206. doi: https://doi.org/.
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Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus. It is a leading cause of visual loss in working-age populations. The clinical management of DR remains challenging. The present study aimed to examine the effect of lutein in the progression of DR and the underlying molecular mechanism(s) using the Ins2Akita mice, a mouse model of type 1 diabetes.
Male heterozygous Ins2Akita mice and their age-matched wild type (WT) littermates were used. Hyperglycemia was confirmed by blood glucose>250 mg/dL. Mice were sacrificed at 26 or 36 weeks of age and retinal protein lysates was collected. Western blot analysis was used to assess for changes in level of autophagy with an anti-LC3 antibody and vascular integrity using an anti-occludin antibody. Moreover, Lutein (4.2mg/kg) was administered to the animals starting 6 weeks of age daily in drinking water, with animals receiving drinking water only as vehicle controls. Electroretinography (ERG) was performed in 26-weeks old mice to evaluate retinal function.
The mean blood glucose in Ins2Akita mice was significantly elevated when compared with their WT littermates. Western blot results showed that LC3II/I expression was up-regulated in 26-week old Ins2Akita mouse retina when compared with the WT controls. Decreased occludin expression was detected in the Ins2Akita mouse retinas when compared with the WT controls at 36 weeks of age. ERG test results showed that Ins2Akita mice displayed lower a-wave and b-wave amplitudes at the age of 26 weeks when compared with the WT controls. However, a significant recovery in both a-wave and b-wave amplitudes was observed in the lutein-treated Ins2Akita mice when compared with the vehicle controls.
Up-regulation of LC3II/I in the Ins2Akita mouse retina suggested potential involvement of the autophagy pathway in the progression of DR. Decreased expression of occludin in the Ins2Akita mouse retina suggested the presence of microvascular injury and leakage under chronic hyperglycemia. Further investigation of this pathway may provide targets for the development of early interventions for DR. Most importantly, preservation of retinal function in the Ins2Akita mice after lutein administration indicated that lutein may be an effective treatment strategy for patients with early DR.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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