Vitamin D in the Cornea and Anterior Segment of the Eye

说明(申请人提供)：维生素D3(VitD)及其代谢物在与健康相关的研究中受到越来越多的关注，因为它们在许多细胞功能中发挥作用，包括细胞分化和基质更新。人体合成维生素D的主要途径是通过阳光对皮肤进行紫外线-B辐射。我们建议研究角膜中维生素D的合成和代谢，角膜是少数几个接受直接UV-B辐射的其他组织之一。我们假设维生素D和维生素D的代谢物存在于角膜和前房中，它们都可以在角膜中合成并通过循环进入前房。我们还假设维生素D代谢产物可以影响角膜上皮细胞的分化。初步数据支持这些假设。R-21应用的具体目的是检验这些假说，包括：(1)确定房水中维生素D和1，25-(OH)2D的存在是否受膳食维生素D摄入和/或紫外线照射的影响；(2)确定11-羟基酶在角膜中的来源(S)；以及(3)确定1，25-(OH)2D活性对于角膜伤口愈合过程中上皮伤口覆盖和再分化是否重要。动物研究将利用基因敲除的小鼠模型以及饮食中维生素D的减少和补充来探索角膜维生素D的代谢和细胞分化。细胞培养研究将用于研究角膜细胞合成维生素D，以及维生素D代谢产物对上皮屏障功能的影响。这项工作的长期目标是为未来眼睛中维生素D的研究奠定基础。我们计划在这项工作的基础上推出R01应用程序，以开展这项未来的维生素D研究。公共卫生相关性最近的研究表明，超过50%的美国人口患有维生素D(VitD)不足。在数以万计的研究维生素D的出版物中，只有少数几篇研究了角膜和眼前段的维生素D，没有一篇研究实际的维生素D浓度、新陈代谢或活性。通过测量角膜和眼睛前段的这些参数，以及维生素D如何影响这一组织中的细胞分化，这项工作为未来的眼睛维生素D工作奠定了基础。

DESCRIPTION (provided by applicant): Vitamin D3 (Vit D) and its metabolites have been receiving increasing attention in health-related studies due to their role in numerous cellular functions, including cell differentiation and matrix turnover. The primary route for Vit D synthesis in the human body is through UV-B irradiation of the skin via sunlight. We propose to study Vit D synthesis and metabolism in the cornea, one of the few other tissues that receives direct UV-B irradiation. We hypothesize that Vit D and Vit D metabolites are present in the cornea and anterior chamber, and that they can be both synthesized in the cornea and can enter the anterior chamber via the circulation. We also hypothesize that Vit D metabolites can influence corneal epithelial cell differentiation. Preliminary data supports these hypotheses. The Specific Aims of this R-21 application are designed to test these hypotheses, and include: (1) Determine if the presence of Vit D and 1,25-(OH)2D in the aqueous humor are influenced by dietary Vit D intake and/or UV exposure; (2) Localize the source(s) of 11-hydroxylase in the cornea; and (3) Determine if 1,25-(OH)2D activity is important for epithelial wound coverage and re-differentiation during corneal wound healing. Animal studies will be performed utilizing knockout mouse models as well as dietary Vit D reduction and supplementation to explore corneal Vit D metabolism and cell differentiation. Cell culture studies will be employed to study Vit D synthesis by corneal cells, as well as the influence of Vit D metabolites on epithelial barrier function. The long term goal of this work is to lay a foundation for future studies of Vit D in the eye. We plan to follow up this work with an R01 application to carry out this future Vit D research. PUBLIC HEALTH RELEVANCE Recent work suggests that more than 50% of the US population suffers from Vitamin D (Vit D) insufficiency. Of the tens of thousands of publications examining Vit D, only a handful has examined Vit D in the cornea and anterior segment, and none of these looked at actual Vit D concentrations, metabolism, or activity. By measuring these parameters in the cornea and anterior segment of the eye, along with how Vit D affects cell differentiation in this tissue, this work set the foundation for future Vit D work in the eye.