CONTROL OF CONJUNCTIVAL GOBLET CELL MUCOUS PRODUCTION

结膜杯状细胞粘液产生的控制

基本信息

批准号：
3266411
负责人：
Darlene A Dartt
金额：
$ 13.74万
依托单位：
SCHEPENS EYE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-05-01 至 1994-04-30
项目状态：
已结题

项目摘要

Conjunctival goblet cells provide the major source of the mucous layer of the tear film. Little is known about the control of mucous production from these goblet cells. The long-term objective of the project is to describe in detail the neuroendocrine control of conjunctival goblet cell synthesis and secretion. Specifically, development of an in vitro preparation to study conjunctival goblet cell secretion will be continued, and development of an in vitro preparation to study synthesis and secretion will be begun. These preparations will be used to determine the short- and long-term neuroendocrine stimuli and inhibitors of mucous synthesis and secretion by goblet cells. For in vivo experiments, drops containing experimental compounds will be applied to the ocular surface of anesthetized rats. Rats will be sacrificed, buttons of conjunctiva removed, and goblet cells stained histochemically and counted. A decrease in goblet cell density will be interpreted as an increase in goblet cell secretion. For in vitro experiments, conjunctiva will be removed from anesthetized rats and placed in short-term culture. Mucous synthesis and secretion will be determined isotopically by incorporating 14[C]-glucosamine into mucous. To determine the neuroendocrine control of goblet cell mucous production, the two preparations will be incubated with neurotransmitters, biologically active peptides, permeable second messengers, eicosanoids, or peptide and steroid hormones. Secretagogues found to affect goblet cells will be characterized pharmacologically. Knowledge of the neuroendocrine control of conjunctival goblet cell mucous production will provide a scientific basis for the development of drugs to treat diseases of mucous underproduction (keratoconjunctivitis sicca, Stevens-Johnson syndrome, thermal injuries, vitamin A deficiency) and mucous overproduction (vernal conjunctivitis, giant papillary conjunctivitis, anesthetic cornea).

结膜杯状细胞提供了粘液层的主要来源撕裂电影。关于粘液的控制知之甚少这些杯状细胞生产。长期目标项目将详细描述神经内分泌的控制结膜杯状细胞合成和分泌。具体来说，开发研究结膜杯细胞的体外准备分泌将继续，并开发体外准备研究合成和分泌将开始。这些准备工作会用于确定短期和长期神经内分泌刺激和杯状细胞粘液合成和分泌的抑制剂。为in 体内实验，含有实验化合物的滴剂将是应用于麻醉大鼠的眼表面。老鼠会牺牲了，切除结膜的按钮，杯状细胞染色组织化学和计数。杯状细胞密度的降低将是被解释为杯状细胞分泌的增加。用于体外实验，结膜将从麻醉大鼠中删除，放置在短期文化中。粘液合成和分泌将是通过将14 [c] - 葡萄糖胺掺入粘液中，以同位素确定。确定杯状细胞粘液的神经内分泌控制生产，这两个制剂将与神经递质，生物活性肽，可渗透的第二信使，eicosanoids或肽和类固醇激素。秘密发现会影响杯状细胞的药理特征。对神经内分泌控制的知识粘液生产将为科学依据开发药物以治疗粘液生产疾病（Sicca角膜结膜炎，史蒂文斯 - 约翰逊综合征，热损伤，维生素A缺乏症）和粘液过量（春季结膜炎，巨型乳头状结膜炎，麻醉角膜）。