Investigation of the capacity of a diet rich in lutein and zeaxanthin (from selected Capsicum varieties) to increase macular pigment density

在发达国家，AMD是导致失明的主要原因。在AMD早期，废物物质--玻璃体--在视网膜下堆积，视网膜是眼睛中的光探测层。玻璃体大小和数量的增加与晚期AMD的发展有关：地理性萎缩(GA)，光检测细胞逐渐死亡；新生血管性AMD(NAMD)，脆弱的血管在视网膜下方和视网膜内生长，导致出血。这两种类型都会导致永久性视力丧失，并可能同时发生。目前，治疗NAMD的唯一有效方法是眼部注射，以帮助减少视力损失。目前还没有已知的治疗方法可以阻止GA的发展。黄斑是视网膜的一个特殊部分，调节中央视觉，提供最敏锐的视觉并促进最佳的颜色辨别(Ma等人)。营养素2016)。黄斑色素以黄斑色素光密度(MPOD)衡量，集中在内层和中央层，被认为对AMD具有保护作用。它主要由叶黄素、叶黄素、玉米黄质和中-玉米黄质(由叶黄素原位合成)组成。这些叶黄素在黄斑中的浓度是血液中的1000倍，显示出高选择性。因此，这些叶黄素被认为通过清除活性氧和过滤蓝光，在保护视网膜和视网膜色素上皮免受光引发的氧化损伤方面发挥了重要作用。叶黄素在高密度脂蛋白上运输，高密度脂蛋白相关基因的多态与AMD和血清叶黄素/玉米黄质相关。来自流行病学研究的数据表明，饮食中的叶黄素摄入量与AMD风险呈负相关。在美国进行的AREDS2随机试验，给早期AMD患者补充了包括叶黄素(10毫克)和依黄素(2毫克)的抗氧化剂补充剂。在该研究的第二次分析中，补充叶黄素/玉米黄质可防止叶黄素/玉米黄质摄入量低的个体进展为晚期AMD(Chew等人。《JAMA眼科杂志》2014)。2016年对19项研究的荟萃分析(Ma等人)结果表明，补充叶黄素、玉米黄质和中玉米黄质均可改善AMD患者和健康受试者的MPOD，并存在剂量-反应关系。然而，并不是所有的研究都表明叶黄素/玉米黄质补充剂对MPOD有影响(Korobelnik等人。《美国医学会眼科杂志》2017；林等人。眼科流行病2017年)。拟议的研究将解决这一不确定性(见1c节)。

AMD is the leading cause of blindness in developed countries. In early AMD, waste material - drusen -builds up under the retina, the light-detecting layer in the eye. Increasing size and number of drusen is associated with development of the late forms of AMD: geographic atrophy (GA) where there is gradual death of light-detecting cells and neovascular AMD (nAMD) where fragile blood vessels grow below and into the retina, causing bleeding. Both types lead to permanent vision loss and can occur together. Currently, the only effective treatment for nAMD is eye injections that help reduce vision loss. No known treatments prevent the development of GA. The macula is a specialised part of the retina, mediating central vision, providing the sharpest visual acuity and facilitating the best colour-discrimination (Ma et al. Nutrients 2016). Macular pigment, measured by macular pigment optical density (MPOD), is concentrated in the inner and central layers and is believed to protect against AMD. It is mainly composed of the xanthophylls, lutein, zeaxanthin and meso-zeaxanthin (synthesised in situ from lutein). The concentration of these xanthophylls in the macula is 1000-fold greater than in the blood, demonstrating high selectivity. These xanthophylls are thus believed to play a major role in protecting the retina and retinal pigment epithelium from light-initiated oxidative damage by scavenging reactive oxygen species and filtering blue light. The xanthophylls are transported on HDL and polymorphisms in HDL-related loci have been associated with AMD and serum lutein/zeaxanthin. Data from epidemiological studies suggest that dietary xanthophyll intake is inversely associated with AMD risk. The AREDS2 randomised trial, carried out in the US, supplemented patients with early AMD with an antioxidant supplement that included lutein (10mg) and eaxanthin (2mg). In a secondary analysis of that study, supplementation with lutein/zeaxanthin was protective against progression to late AMD in individuals with low lutein/zeaxanthin intake (Chew et al. JAMA Opthalmol 2014). A 2016 metaanalysis of 19 studies (Ma et al.) showed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects, with a dose-response relationship. However, not all studies have shown an effect of lutein/zeaxanthin supplements on MPOD (Korobelnik et al. JAMA Ophthalmol 2017; Lin et al. Opthalmic Epidemiol 2017). The proposed research will address that uncertainty (see Section 1c).