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Vitamin D in the Cornea and Anterior Segment of the Eye

角膜和眼前节中的维生素 D

基本信息

批准号：
7589875
负责人：
MITCHELL A WATSKY
金额：
$ 22.13万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7589875
关键词：
25-hydroxyvitamin D 7-dehydrocholesterol Affect Animals Anterior Anterior eyeball segment structure Applications Grants Aqueous Humor Attention Binding Blood Circulation Cell Culture Techniques Cell Differentiation process Cell physiology Cells Cholecalciferol Cornea Corneal Injury Culture Media Data Diet Differentiation and Growth Diffusion Dihydroxycholecalciferols Enzymes Epithelial Epithelial Cells Epithelium Eye Foundations Future Goals Grant Histocompatibility Testing Human body In Situ Hybridization In Vitro Intake Keratin Knock-out Knockout Mice Mass Spectrum Analysis Measures Metabolism Mixed Function Oxygenases Mus Oryctolagus cuniculus Phenotype Play Population Process Proteins Publications Research Role Route Serum Skin Source Sun Exposure Sunlight Supplementation Testing Tissues UV Radiation Exposure United States Vitamin D Vitamin D3 Receptor Vitamin Deficiency Work Workplace Wound Healing anterior chamber autocrine corneal epithelium design feeding follow-up in vivo irradiation light microscopy mouse model paracrine public health relevance receptor research study sunglasses wound

项目摘要

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.

描述（由申请人提供）：维生素D3（维生素D）及其代谢产物在健康相关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周转。维生素D在人体内合成的主要途径是通过阳光照射皮肤的UV-B。我们建议研究维生素D的合成和代谢的角膜，少数其他组织之一，直接接受UV-B辐射。我们假设维生素D和维生素D代谢物存在于角膜和前房中，并且它们都可以在角膜中合成，并且可以通过循环进入前房。我们还假设维生素D代谢产物可以影响角膜上皮细胞分化。初步数据支持这些假设。本R-21应用的具体目的旨在检验这些假设，包括：（1）确定房水中维生素D和1，25-（OH）2D的存在是否受饮食维生素D摄入量和/或紫外线暴露的影响;（2）定位角膜中11-羟化酶的来源;和（3）确定1，25-（OH）2D活性对于角膜伤口愈合期间的上皮伤口覆盖和再分化是否重要。将利用基因敲除小鼠模型以及饮食维生素D减少和补充进行动物研究，以探索角膜维生素D代谢和细胞分化。将采用细胞培养研究来研究角膜细胞的维生素D合成，以及维生素D代谢产物对上皮屏障功能的影响。本工作的长期目标是为今后研究维生素D在眼内的作用奠定基础。我们计划通过R 01应用程序来跟进这项工作，以开展未来的维生素D研究。最近的研究表明，超过50%的美国人口患有维生素D（Vit D）不足。在成千上万的研究维生素D的出版物中，只有少数研究了角膜和眼前节中的维生素D，并且没有一个研究了实际的维生素D浓度，代谢或活性。通过测量角膜和眼前节中的这些参数，沿着维生素D如何影响该组织中的细胞分化，这项工作为未来的维生素D在眼睛中的工作奠定了基础。