RETINOIDS AND LACRIMAL GLAND FUNCTION

类维生素A和泪腺功能

• 批准号: 2159509
• 负责人: JOHN L UBELS
• 金额: $ 6.03万
• 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/2159509
• 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.

泪腺在维持健康中起着至关重要的作用 眼表。 泪腺液提供眼表 润滑，抗细菌蛋白，电解质和营养素。 泪腺功能的缺陷为疾病奠定了阶段，例如 角膜结膜炎SICCA，这种疾病在女性中的发生频率比 在男人。开发干眼疾病的理性疗法需要 对正常的泪腺功能的透彻理解。提议 工作将检验泪腺转运的假设， 代谢并分泌了眼表所需的维生素A 上皮和类维生素（维生素A衍生物）是需要的 维持泪腺结构和功能。 拟议研究的具体目的是： 1）表征合成和水解视网膜酯的酶 在泪腺中，强调控制这些酶 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网膜酯的活性 兔和大鼠泪腺中的水解酶，并确定 细胞视黄醇结合蛋白对这些活性的影响 酶。 2）确定是否存在于 泪腺和角膜，并研究类视黄素对 表达这些受体。这将通过探测组织来完成 以及为这些大鼠和兔子的培养细胞 受体，以及通过结合测定法检测受体和 抗体。 3）表征泪腺细胞的功能，重点是 视黄素的作用通过研究视黄酸对生长的影响， 这些细胞在培养中的分化和代谢。这些细胞 还将探测MRNA的类视黄蛋白结合蛋白。 4）表征人类泪腺中的类维生素性代谢。这将是 通过测量视黄酯的活性来完成 代谢并通过探测类视黄素的mRNA的人泪腺 结合蛋白和核受体。这些实验将确认 动物数据与人类泪功能的相关性。 拟议的研究将有助于阐明类视视视网膜的作用 泪腺和眼表功能将有助于 对营养在保持正常的作用的总体理解 想象。