Effect of lutein in early diabetic retinopathy using the Ins2Akita mice

Abstract

Purpose: Diabetic retinopathy (DR), a major microvascular complication of diabetes mellitus, is a leading cause of blindness in the working-age population. The management of DR remains challenging. Early detection and treatment is crucial to delay or prevent visual loss in patients with diabetes. The present study aimed to examine the effect of lutein in early DR using the Ins2Akita mice, a mouse model of type 1 diabetes. Methods: Male heterozygous Ins2Akita mice and their age-matched wild type (WT) littermates were subjected to daily lutein administration in drinking water starting at 6 weeks old until 18, 26 or 36 weeks of age. Plain water served as control. Retinal vascular permeability was examined after retro-orbital FITC-dextran perfusion. Retinal expression of occludin was assessed via Western blots. Microglia were immunolabeled with anti-Iba-1 and anti-CD68 antibodies on flat-mounted retinas and subjected to morphological and quantitative analysis. Retinal thickness was quantified using paraffin-embedded sections. Retinal function was examined by electroretinography (ERG). Results: Increased vascular permeability and decreased occludin expression were detected in 36-week-old Ins2Akita mouse retina when compared with WT controls. Increased microglial reactivity was detected in the 18-week-old Ins2Akita mouse retina when compared with WT controls and was suppressed by lutein treatment. Decreased retinal inner plexiform layer (IPL) thickness was observed in the 36-week-old Ins2Akita mouse when compared with WT controls, which was increased by lutein treatment. ERG results showed lower a-wave and b-wave amplitudes in the 26- and 36-week-old Ins2Akita mice when compared with WT controls. Most importantly, a-wave and b-wave amplitudes were significantly improved in Ins2Akita mice after lutein treatment. Conclusions: Altered retinal vascular permeability and occludin expression suggested microvascular degeneration in Ins2Akita mice, similar to pathological features observed in nonproliferative DR patients. Suppression of microglial reactivity in Ins2Akita mice by lutein suggested an anti-inflammatory role of lutein in the early stage of DR. Increase of retinal IPL thickness and preservation of retinal function in Ins2Akita mice by lutein indicated that lutein administration may be an effective treatment for DR patients.