Beneficial effects of lutein in early diabetic retinopathy using the Ins2Akita mice

Abstract

PURPOSE: Diabetic retinopathy (DR) is a major microvascular complication of diabetes; its management remains challenging. Early detection and treatment is crucial to slow sight deterioration. The effect of lutein in early DR was investigated in Ins2Akita mouse, a type 1 diabetes animal model. METHODS: Lutein was administered to male Ins2Akita mice starting 6 weeks old daily in drinking water until 18, 26 or 36 weeks of age. Plain water and age-matched littermates (wildtype, WT) served as control. Retinal vascular permeability was examined after retro-orbital FITC-dextran perfusion. Retinal expression of occludin was assessed via Western blots. Microglia in the retina were immunolabeled with anti-Iba-1 and anti-CD68 antibodies. 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. 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 DR. Preservation of retinal function in Ins2Akita mice by lutein indicated that lutein administration may be an effective treatment for DR patients.