Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA.
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Nutrients. 2022 Jun 8;14(12):2371. doi: 10.3390/nu14122371.
The systemic transport of dietary vitamin A/all- retinol bound to RBP4 into peripheral tissues for storage is an essential physiological process that continuously provides visual chromophore precursors to the retina under fasting conditions. This mechanism is critical for phototransduction, photoreceptor cell maintenance and survival, and in the support of visual function. While the membrane receptor STRA6 facilitates the blood transport of lipophilic vitamin A into the eye, it is not expressed in most peripheral organs, which are proposed to express a second membrane receptor for the uptake of vitamin A from circulating RBP4. The discovery of a novel vitamin A receptor, RBPR2, which is expressed in the liver and intestine, but not in the eye, alluded to this long-sort non-ocular membrane receptor for systemic RBP4-ROL uptake and transport. We have previously shown in zebrafish that the retinol-binding protein receptor 2 (Rbpr2) plays an important role in the transport of yolk vitamin A to the eye. Mutant zebrafish lines manifested in decreased ocular retinoid concentrations and retinal phenotypes. To investigate a physiological role for the second vitamin A receptor, RBPR2, in mammals and to analyze the metabolic basis of systemic vitamin A transport for retinoid homeostasis, we established a whole-body knockout mouse () model. These mice were viable on both vitamin A-sufficient and -deficient diets. mice that were fed a vitamin A-sufficient diet displayed lower ocular retinoid levels, decreased opsins, and manifested in decrease visual function, as measured by electroretinography. Interestingly, when mice were fed a vitamin A-deficient diet, they additionally showed shorter photoreceptor outer segment phenotypes, altogether manifesting in a significant loss of visual function. Thus, under conditions replicating vitamin A sufficiency and deficiency, our analyses revealed that RBPR2-mediated systemic vitamin A transport is a regulated process that is important for vitamin A delivery to the eye when RBP4-bound ROL is the only transport pathway in the fasting condition or under vitamin A deficiency conditions.
视黄醇结合蛋白 4（RBP4）结合的全反式视黄醇（all- retinol bound to RBP4）与膳食维生素 A 一道经系统转运至外周组织以供储存，这是一个基本的生理过程，它在禁食条件下不断向视网膜提供视觉色素前体。该机制对视黄醛的光转导、感光细胞的维持和存活以及视觉功能的支持至关重要。尽管跨膜受体 STRA6 促进亲脂性维生素 A 从血液转运至眼睛，但它在大多数外周组织中并不表达，这些组织被认为表达了第二种细胞膜受体，用于从循环 RBP4 摄取维生素 A。新型维生素 A 受体 RBPR2 的发现表明，这种受体在肝脏和肠道中表达，但不在眼睛中表达，这暗示了该长链非眼部细胞膜受体用于全身 RBP4-ROL 的摄取和转运。我们之前在斑马鱼中表明，视黄醇结合蛋白受体 2（Rbpr2）在卵黄维生素 A 向眼睛的转运中发挥着重要作用。突变的斑马鱼系表现出眼部类视黄醇浓度降低和视网膜表型改变。为了研究第二种维生素 A 受体 RBPR2 在哺乳动物中的生理作用，并分析全身维生素 A 转运的代谢基础以维持类视黄醇稳态，我们建立了全身性 RBPR2 基因敲除（）小鼠模型。这些小鼠在维生素 A 充足和缺乏的饮食条件下均可存活。给予维生素 A 充足饮食的 RBPR2 基因敲除小鼠表现出较低的眼部类视黄醇水平、视蛋白减少，并表现出电生理视网膜电图（ERG）检测到的视觉功能下降。有趣的是，当 RBPR2 基因敲除小鼠给予维生素 A 缺乏饮食时，它们还表现出较短的光感受器外节表型，这总体现为视觉功能显著丧失。因此，在模拟维生素 A 充足和缺乏的条件下，我们的分析表明，RBPR2 介导的全身维生素 A 转运是一个受调控的过程，当 RBP4 结合的视黄醇是禁食状态或维生素 A 缺乏状态下唯一的转运途径时，该过程对于维生素 A 向眼睛的输送非常重要。
