Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois, Chicago, IL, 60612, USA.
Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL, 60612, USA.
Sci Rep. 2023 Jun 6;13(1):9179. doi: 10.1038/s41598-023-36268-0.
Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD, abnormalities in visual functions often precede them, and are increasingly being used as diagnostic and prognostic markers for the disease. Retina contains the highest concentration of the essential fatty acid docosahexaenoic acid (DHA) in the body, and its deficiency is associated with several retinal diseases including diabetic retinopathy and age related macular degeneration. In this study, we tested the hypothesis that enriching retinal DHA through a novel dietary approach could ameliorate symptoms of retinopathy in 5XFAD mice, a widely employed model of AD. The results show that 5XFAD mice have significantly lower retinal DHA compared to their wild type littermates, and feeding the lysophosphatidylcholine (LPC) form of DHA and eicosapentaenoic acid (EPA) rapidly normalizes the DHA levels, and increases retinal EPA by several-fold. On the other hand, feeding similar amounts of DHA and EPA in the form of triacylglycerol had only modest effects on retinal DHA and EPA. Electroretinography measurements after 2 months of feeding the experimental diets showed a significant improvement in a-wave and b-wave functions by the LPC-diet, whereas the TAG-diet had only a modest benefit. Retinal amyloid β levels were decreased by about 50% by the LPC-DHA/EPA diet, and by about 17% with the TAG-DHA/EPA diet. These results show that enriching retinal DHA and EPA through dietary LPC could potentially improve visual abnormalities associated with AD.
阿尔茨海默病（AD）是老年人中最常见的痴呆症病因。尽管认知和记忆受损是 AD 的最突出特征，但视觉功能异常通常先于这些特征出现，并且越来越多地被用作该疾病的诊断和预后标志物。视网膜含有体内必需脂肪酸二十二碳六烯酸（DHA）的最高浓度，其缺乏与几种视网膜疾病有关，包括糖尿病性视网膜病变和年龄相关性黄斑变性。在这项研究中，我们通过一种新的饮食方法来测试通过富集视网膜 DHA 可以改善 5XFAD 小鼠（AD 的广泛应用模型）的视网膜病变症状的假设。结果表明，5XFAD 小鼠的视网膜 DHA 明显低于其野生型同窝仔鼠，并且饲喂溶血磷脂酰胆碱（LPC）形式的 DHA 和二十碳五烯酸（EPA）可迅速使 DHA 水平正常化，并使视网膜 EPA 增加数倍。另一方面，以三酰基甘油形式饲喂等量的 DHA 和 EPA 对视网膜 DHA 和 EPA 仅具有适度的影响。饲喂实验饮食 2 个月后的视网膜电图测量显示，LPC 饮食可显著改善 a 波和 b 波功能，而 TAG 饮食仅具有适度的益处。LPC-DHA/EPA 饮食可使视网膜淀粉样β水平降低约 50％，而 TAG-DHA/EPA 饮食可降低约 17％。这些结果表明，通过饮食 LPC 富集视网膜 DHA 和 EPA 可能有助于改善与 AD 相关的视觉异常。
