摘要
Accumulation of bisretinoids such as A2E and its isomer iso-A2E is thought to mediate blue light-induced oxidative damage associated with age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). We hypothesize that increasing dietary intake of the macular carotenoids lutein and zeaxanthin in individuals at risk of AMD and STGD1 can inhibit the formation of bisretinoids A2E and iso-A2E, which can potentially ameliorate macular degenerative diseases. To study the beneficial effect of macular carotenoids in a retinal degenerative diseases model, we used ATP-binding cassette, sub-family A member 4 (Abca4−/−)/β,β-carotene-9′,10′-oxygenase 2 (Bco2−/−) double knockout (KO) mice that accumulate elevated levels of A2E and iso-A2E in the retinal pigment epithelium (RPE) and macular carotenoids in the retina. Abca4−/−/Bco2−/− and Abca4−/− mice were fed a lutein-supplemented chow, zeaxanthin-supplemented chow or placebo chow (~2.6 mg of carotenoid/mouse/day) for three months. Visual function and electroretinography (ERG) were measured after one month and three months of carotenoid supplementation. The lutein and zeaxanthin supplemented Abca4−/−/Bco2−/− mice had significantly lower levels of RPE/choroid A2E and iso-A2E compared to control mice fed with placebo chow and improved visual performance. Carotenoid supplementation in Abca4−/− mice minimally raised retinal carotenoid levels and did not show much difference in bisretinoid levels or visual function compared to the control diet group. There was a statistically significant inverse correlation between carotenoid levels in the retina and A2E and iso-A2E levels in the RPE/choroid. Supplementation with retinal carotenoids, especially zeaxanthin, effectively inhibits bisretinoid formation in a mouse model of STGD1 genetically enhanced to accumulate carotenoids in the retina. These results provide further impetus to pursue oral carotenoids as therapeutic interventions for STGD1 and AMD.
摘要译文
诸如A2E及其异构体ISO-A2E的Bisretinoids的积累被认为是介导与年龄相关的黄斑变性（AMD）和常染色体隐性晕术（STGD1）相关的蓝光诱导氧化损伤。我们假设随着AMD和STGD1风险的患者中，增加膳食类叶黄素和玉米黄素的膳食摄入量，可以抑制Bisretinoids A2E和ISO-A2E的形成，这可能会改善黄斑的退行性疾病。为了研究黄斑类胡萝卜素在视网膜退行性疾病模型中的有益效果，我们使用ATP结合盒，子族构件4（ABCA4 - / - / - / - / - / - / - / - ）/β，β-胡萝卜素-9' ，10'-氧合酶2（BCO2 - / - / - / - / - / - / sup>）双敲除（KO）小鼠，其在视网膜颜料上皮（RPE）和视网膜中的黄斑类药物和黄斑类胡萝卜素中累积升高的A2e和ISO-A2E水平。 ABCA4 - / - / bco2 - / - / sup>和abca4 - / - 小鼠用叶黄素补充的食物，Zeaxanthin补充的食物或安慰剂味道（〜2.6毫克类胡萝卜素/鼠标/日）三个月。在一个月和三个月的类胡萝卜素补充后测量视觉功能和电动仪造影（ERG）。补充了ABCA4 - / - / - / - / - / - / sup>小鼠的叶黄素和玉米蛋白和Zeaxanthin，与用安慰剂饲喂的小鼠相比，RPE / Choroid A2e和ISO-A2e的含量显着降低了较低的RPE / Choroid A2E和ISO-A2E提高视觉性能。与对照饮食组相比，ABCA4 - / - / sup>小鼠小鼠小鼠的小鼠微小的视网膜类动物骨水平，并且与对照饮食组相比，在对照组水平或视觉功能上没有显示出大量差异。在RPE /脉络膜中的视网膜和A2e和ISO-A2E水平之间存在统计学上显着的反比相关性。用视网膜类胡萝卜素的补充，特别是玉米蛋白，有效地抑制STGD1的小鼠模型中的Bisretinoid形成，以累积在视网膜中的类胡萝卜素。这些结果提供了进一步推动口服类胡萝卜素作为STGD1和AMD的治疗干预措施。
RanganathanArunkumar[a];ArunaGorusupudi[a];BinxingLi[a];J. DavidBlount[a];UzoamakaNwagbo[a];Hye JinKim[b][c];Janet R.Sparrow[b][c]. Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4−/−/Bco2−/− double knockout mice[J]. Experimental Eye Research, 2021,209