CONTROL OF CONJUNCTIVAL GOBLET CELL MUCOUS PRODUCTION

结膜杯状细胞粘液产生的控制

• 批准号: 3266409
• 负责人: Darlene A Dartt
• 金额: $ 13.31万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/3266409
• 关键词: calcium; conjunctiva; cyclic AMP; cyclic GMP; denervation; eicosanoids; epidermal growth factor; glycoprotein biosynthesis; growth factor; laboratory rat; leukotrienes; mucins; mucus; neuroendocrine system; neurotransmitters; protein kinase C; radiotracer; second messengers; secretion; steroid hormone; stimulant /agonist; tear; tetrodotoxin; tissue /cell culture

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).

结膜杯状细胞是粘液层的主要来源 泪膜的颜色。对粘液的控制知之甚少 从这些高脚杯细胞中产生。该计划的长远目标 项目是详细描述神经内分泌控制 结膜杯状细胞的合成和分泌。具体来说， 结膜杯状细胞体外研究制剂的研制 将继续分泌，并开发一种体外制剂 将开始研究合成和分泌。这些准备工作将 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物。For In 体内实验，含有实验化合物的水滴将被 应用于麻醉大鼠的眼表。老鼠将会是 处死，摘除结膜纽扣，高脚杯细胞染色 组织化学和计数。高脚杯细胞密度的降低将是 解释为杯状细胞分泌增加。用于体外实验 实验，将麻醉大鼠的结膜摘除并 被置于短期文化中。粘液的合成和分泌将 通过将14[C]-氨基葡萄糖掺入粘液中进行同位素测定。 确定杯状细胞粘液的神经内分泌控制 生产，这两种制剂将与孵化 神经递质，生物活性多肽，渗透性秒 信使、二十烷基类或多肽和类固醇激素。分泌者 被发现影响杯状细胞的药物将具有药理学特征。 结膜杯状细胞神经内分泌调控的认识 粘液的生产将为今后的研究提供科学依据 治疗粘液分泌不足疾病的药物研究进展 (干性角膜结膜炎，Stevens-Johnson综合征，热损伤， 维生素A缺乏)和粘液分泌过剩(春季结膜炎、 巨乳头性结膜炎、麻醉性角膜)。