RETINOIDS AND LACRIMAL GLAND FUNCTION

类维生素A和泪腺功能

• 批准号: 2159507
• 负责人: JOHN L UBELS
• 金额: $ 18.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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/2159507
• 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

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.

泪腺对于维持人体健康起着至关重要的作用 眼表。 泪腺液提供眼表 具有润滑、抗菌的蛋白质、电解质和营养成分。 泪腺功能缺陷为疾病奠定了基础，例如 干燥性角结膜炎，一种女性发病率高于女性的疾病 在男性中。干眼病合理治疗的发展需要 彻底了解正常泪腺功能。拟议的 这项工作将检验泪腺运输的假设， 代谢并分泌眼表所需的维生素A 上皮细胞和类维生素A（维生素A衍生物）是 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，重点是通过以下方式控制这些酶 细胞视黄醇结合蛋白。 这将通过测量来完成 卵磷脂的活性：视黄醇酰基转移酶和视黄酯 家兔和大鼠泪腺水解酶的测定 细胞视黄醇结合蛋白对这些活性的影响 酶。 2) 确定细胞核中是否存在视黄酸受体 泪腺和角膜并研究类维生素A对泪腺和角膜的影响 表达这些受体。这将通过探测组织来完成 以及大鼠和兔的培养细胞以获取这些的信使RNA 受体，以及通过结合测定法检测受体 抗体。 3）表征泪腺细胞的功能，重点是 通过研究视黄酸对生长的影响来了解类视黄醇的作用， 这些细胞在培养物中的分化和代谢。这些细胞 还将探测类维生素A结合蛋白的mRNA。 4) 表征人类泪腺中类视黄醇代谢的特征。这将是 通过测量视黄酯酶的活性来完成 代谢并通过探测人类泪腺中的视黄醇 mRNA 结合蛋白和核受体。这些实验将证实 动物数据与人类泪腺功能的相关性。 拟议的研究将有助于阐明类视黄醇在 泪腺和眼表功能，从而有助于 对营养在维持正常状态中的作用的整体了解 想象。