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 specialized in the secretion of aqueous humor fluid and the regulation of intraocular pressure. In this study, we report on the expression of the regulatory peptide neurotensin (NT) and a set of differentiated neuroendocrine markers including neurotensin receptors (NTrs), the prohormone convertases furin, PC1, and PC2, and the neuroendocrine polypeptide 7B2 in the ciliary epithelium. Using a human cell line, ODM-2, derived from the nonpigmented ciliary epithelium, we demonstrate that (1) NT expression is highly activated by nerve growth factor, glucocorticoid, and activators of adenylate cyclase; (2) NTr expression is up-regulated by selective ligand-activated beta2-adrenergic receptor; and (3) PC1 and PC2 expression are up-regulated via distinct signaling transduction pathways. PC1 gene expression is activated by phorbol ester, and PC2 by the same inducers as those of NT expression. A radioimmunoassay for NT detected an NT-like immunoreactivity in human ciliary epithelium and ODM-2 cell extracts, in aqueous humor, and in conditioned culture medium. The results support the view that the entire ciliary epithelium functions as a neuroendocrine tissue, synthesizing, processing, and releasing NT into the aqueous humor where it may exert important physiological functions through autocrine and/or paracrine mechanisms.
Ortego
J
J
Yale University School of Medicine, Department of Ophthalmology and Visual Science, New Haven, Connecticut 06510, U.S.A.
Coca-Prados
M
M
D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D002460:Cell Line; D002924:Ciliary Body / Q000166:cytology / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D045683:Furin; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000378:metabolism; D009496:Neurotensin / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D018028:Receptors, Neurotensin / Q000096:biosynthesis*; D013381:Subtilisins / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013999:Timolol / Q000494:pharmacology; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects
D017931:DNA Primers; D009414:Nerve Growth Factors; D018028:Receptors, Neurotensin; D005576:Colforsin; D009496:Neurotensin; D003907:Dexamethasone; D013999:Timolol; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate