Long-term lutein administration attenuates retinal inflammation and functional deficits in early diabetic retinopathy using the Ins2 Akita/+ mice

Abstract

Introduction Lutein is a carotenoid whose protective effects in the retina have been reported in various studies. The effect of lutein has not been reported in the retina of the Ins2 Akita/+ mouse, a well-characterized genetic model for diabetic retinopathy (DR) in which the etiology of diabetes is better defined than the chemically induced diabetes. The objective of the present study is to investigate the effect of long-term administration of lutein in early stages of DR using the Ins2 Akita/+ mouse. Research design and methods Heterozygous male Ins2 Akita/+ and age-matched wild-type mice were used. Lutein was administered to the mice in drinking water starting 6 weeks old daily until analysis at 4.5, 6.5 or 9 months of age. Plain water served as non-treatment control. Microglia were immunostained with ionized calcium-binding adapter molecule 1 (Iba-1) and cluster of differentiation 68 (CD68) in retinal flat-mounts. Vascular endothelial growth factor (VEGF) level in the retina was assessed by enzyme-linked immunosorbent assay (ELISA). Vascular permeability was analyzed in retinal flat-mounts after fluorescein isothiocyanate (FITC)-dextran perfusion. Retinal occludin expression was assessed via Western blots. Retinal function was examined by electroretinography (ERG). Results Increased microglial reactivity was detected in the Ins2 Akita/+ mouse retina and was suppressed by lutein. Lutein administration also reduced the upregulation of VEGF in the Ins2 Akita/+ mouse retina. Increased vascular leakage and decreased occludin expression were observed in the Ins2 Akita/+ mouse retina, and these alterations were attenuated by lutein treatment. ERG recordings showed reduced a-wave and b-wave amplitudes in the Ins2 Akita/+ mice. With lutein treatment, the ERG deficits were significantly alleviated. Conclusions We showed beneficial effects of long-term lutein administration in the Ins2 Akita/+ mouse retina, including suppression of retinal inflammation, protection of retinal vasculature and preservation of retinal function. These results point to lutein's potential as a long-term therapeutic intervention for prevention of inflammation and retinal degeneration in patients with early DR.