THE ROLE OF RETINOIDS IN LACRIMAL GLAND FUNCTION

泪腺在维持眼表健康方面起着至关重要的作用。泪腺液为眼睛表面提供润滑剂、抗菌蛋白质、电解质和营养物质。泪腺功能缺陷为干燥性角结膜炎等疾病的发生奠定了基础，干燥性角结膜炎是一种女性多于男性的疾病。开发合理的干眼病治疗方法需要对正常泪腺功能有透彻的了解。这项拟议的工作将检验以下假设：泪腺运输、代谢和分泌眼表上皮所需的维生素A，以及维甲酸(维生素A衍生物)是维持泪腺结构和功能所必需的。拟议研究的具体目的是：L)表征泪腺中合成和水解视黄酯的酶，重点是细胞视黄醇结合蛋白对这些酶的控制。这将通过测量兔和大鼠泪腺中卵磷脂：视黄醇酰基转移酶和视黄酯水解酶的活性，并确定细胞视黄醇结合蛋白对这些酶活性的影响来实现。2)确定泪腺和角膜中是否存在维甲酸核受体，并研究维甲酸对这些受体表达的影响。这将通过探测大鼠和兔子的组织和培养细胞中这些受体的信使RNA，并通过结合分析和抗体来检测受体来完成。3)通过研究维甲酸对泪腺细胞生长、分化和代谢的影响，确定泪腺细胞的功能，重点研究维甲酸在泪腺细胞中的作用。这些细胞还将被探测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。这将通过测量视黄酯代谢酶的活性以及探测人类泪腺中的视黄醇结合蛋白和核受体的mRNA来实现。这些实验将肯定动物数据与人类泪液功能的相关性。这项研究将有助于阐明维甲酸在泪腺和眼表功能中的作用，从而有助于全面了解营养在维持正常视力中的作用。

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: l) 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.