RETINOIDS AND LACRIMAL GLAND FUNCTION

类维生素A和泪腺功能

• 批准号: 2019499
• 负责人: JOHN L UBELS
• 金额: $ 15万
• 依托单位: CALVIN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019499
• 关键词: acyltransferase; antireceptor antibody; biological transport; cell adhesion molecules; cell differentiation; cell growth regulation; corneal epithelium; corneal stroma; cytoskeleton; enzyme activity; hydrolase; laboratory rabbit; laboratory rat; lacrimal apparatus; nucleoproteins; nutrition related tag; receptor binding; receptor expression; retinoid binding proteins; retinoids; tear; tissue /cell culture; vitamin metabolism; vitamin receptor

The lacrimal glands play an essential role in maintenance of the health of the ocular surface. The lacrimal gland fluid provides the ocular surface with lubrication, anti-bacterial proteins, electrolytes and nutrients. Deficits in lacrimal gland function set the stage for diseases, such as keratoconjunctivitis sicca, a disease that occurs more often in women than in men. The development of rational therapy for dry eye diseases requires a thorough understanding of normal lacrimal gland function. The proposed work will test the hypotheses that the lacrimal gland transports, metabolizes and secretes vitamin A which is required by the ocular surface epithelium and that retinoids (vitamin A derivatives) are required for maintenance of lacrimal gland structure and function. The specific aims of the proposed research are to: 1) characterize the enzymes that synthesize and hydrolyse retinyl esters in the lacrimal gland with emphasis of the control of these enzymes by cellular retinol binding protein. This will be accomplished by measuring the activity of lecithin:retinol acyltransferase and retinyl ester hydrolase in lacrimal glands of rabbits and rats and determining the effects of cellular retinol binding protein on the activity of these enzymes. 2) Determine whether nuclear retinoic acid receptors are present in the lacrimal gland and cornea and to study the effect of retinoids on the expression these receptors. This will be accomplished by probing tissues and cultured cells of rats and rabbits for the messenger RNA for these receptors, and detection of the receptors by binding assays and antibodies. 3) Characterize the function of lacrimal gland cells with emphasis on the role of retinoids by studying the effects of retinoic acid on the growth, differentiation, and metabolism of these cells in culture. These cells will also be probed for the mRNA for retinoid binding protein. 4) Characterize retinoid metabolism in human lacrimal gland. This will be accomplished by measurement of the activity of enzymes of retinyl ester metabolism and by probing the human lacrimal gland for mRNA for retinoid binding proteins and nuclear receptors. These experiments will affirm the relevance of the animal data to human lacrimal function. The proposed research will help to elucidate the role of retinoids in lacrimal gland and ocular surface function and thereby will contribute to the overall understanding of the role of nutrition in maintaining normal vision.

泪腺在维持人的健康方面起着至关重要的作用 眼表。泪腺液体提供眼表 含有润滑剂、抗菌蛋白质、电解液和营养素。 泪腺功能缺陷为疾病奠定了基础，例如 干燥性角结膜炎是一种女性比女性更常见的疾病 在男人身上。干眼病合理治疗的发展要求 对泪腺功能有透彻的了解。建议数 这项工作将测试泪腺运输的假说， 代谢和分泌眼表所需的维生素A 上皮细胞和维甲酸(维生素A衍生物)是必需的 维持泪腺结构和功能。 拟议研究的具体目标是： 1)表征合成和水解视黄酯的酶 在泪腺中，强调这些酶的控制 细胞视黄醇结合蛋白。这将通过测量来实现 卵磷脂：视黄醇酰基转移酶和视黄酯的活性 兔泪腺和大鼠泪腺水解酶活性的测定 细胞视黄醇结合蛋白对这些酶活性的影响 酵素。 2)确定核维甲酸受体是否存在于 目的：探讨维甲酸对大鼠泪腺和角膜的影响。 表达这些受体。这将通过探测组织来完成 和培养的大鼠和兔的细胞，以获得这些基因的信使RNA 受体，并通过结合试验和 抗体。 3)描述泪腺细胞的功能，重点是 维甲酸的作用通过研究维甲酸对生长的影响 这些细胞在培养中的分化和代谢。这些细胞 还将探索视黄醇结合蛋白的信使核糖核酸。 4)人泪腺类维A酸代谢的研究。这将是 通过测量视黄酸酯酶的活性来实现 新陈代谢和通过探测人泪腺中类维甲酸的mRNA 结合蛋白和核受体。这些实验将肯定 动物数据与人类泪液功能的相关性。 这项拟议的研究将有助于阐明维甲酸在 泪腺和眼表功能，从而有助于 对营养在维持正常中的作用的全面认识 幻象。