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).
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