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。泪腺液为眼表提供润滑、抗菌蛋白、电解质和营养物质。泪腺功能的缺陷为疾病提供了条件，如镰状角膜结膜炎，这种疾病在女性中比在男性中更常见。干眼病的合理治疗需要对正常泪腺功能有透彻的了解。本研究将验证以下假设：泪腺运输、代谢和分泌眼表上皮所需的维生素A，以及类维生素A（维生素A衍生物）是维持泪腺结构和功能所必需的。本研究的具体目的是：1)表征泪腺中合成和水解视黄醇酯的酶，重点研究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醇酯水解酶的活性来完成，并确定细胞视黄醇结合蛋白对这些酶活性的影响。2)确定泪腺和角膜中是否存在核维甲酸受体，研究类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来获得这些受体的信使RNA，并通过结合试验和抗体来检测受体。3)通过研究视黄酸对泪腺细胞生长、分化和代谢的影响，表征泪腺细胞的功能，重点研究类视黄酸的作用。这些细胞也将探测类视黄醛结合蛋白的mRNA。4)表征人泪腺类视黄醇代谢。这将通过测量视黄醇酯代谢酶的活性和探测人类泪腺中视黄醇结合蛋白和核受体的mRNA来完成。这些实验将肯定动物数据与人类泪腺功能的相关性。本研究将有助于阐明类维生素a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.