MOLECULAR CHARACTERIZATION AND DIFFERENTIAL GENE INDUCTION OF THE NEUROENDOCRINE-SPECIFIC GENES NEUROTENSIN, NEUROTENSIN RECEPTOR, PC1, PC2, AND 7B2 IN THE HUMAN OCULAR CILIARY EPITHELIUM

The ocular ciliary epithelium is a bilayer of neuroepithelial cells sp ecialized in the secretion of aqueous humor fluid and the regulation o f intraocular pressure. In this study, we report on the expression of the regulatory peptide neurotensin (NT) and a set of differentiated ne uroendocrine markers including neurotensin receptors (NTrs),the prohor mone convertases furin, PCI, and PC2, and the neuroendocrine polypepti de 7B2 in the ciliary epithelium, Using a human cell line, ODM-2, deri ved from the nonpigmented ciliary epithelium, we demonstrate that (1) NT expression is highly activated by nerve growth factor, glucocortico id, and activators of adenylate cyclase; (2) NTr expression is up-regu lated by selective ligand-activated beta(2)-adrenergic receptor; and ( 3) PC1 and PC2 expression are up-regulated via distinct signaling tran sduction pathways, PC1 gene expression is activated by phorbol ester, and PC2 by the same inducers as those of NT expression, A radioimmunoa ssay for NT detected an NT-like immunoreactivity in human ciliary epit helium and ODM-2 cell extracts, in aqueous humor, and in conditioned c ulture medium, The results support the view that the entire ciliary ep ithelium functions as a neuroendocrine tissue, synthesizing, processin g, and releasing NT into the aqueous humor where it may exert importan t physiological functions through autocrine and/or paracrine mechanism s.