Molecular Characterization and Differential Gene Induction of the Neuroendocrine‐Specific Genes Neurotensin, Neurotensin Receptor, PC1, PC2, and 7B2 in the Human Ocular Ciliary Epithelium

Abstract

Abstract: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 convertasesfurin, PCi, 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 ,3 2-adrenergic receptor; and (3) PCi and PC2 expression are up-regulated via distinct signaling transduction pathways. PCi 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.

Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles

“…Some of these peptides, synthesized and released by the ciliary epithelium, are neuropeptides and hormones usually restricted to endocrine tissues and cells (Ortego et al, 1996a,b;Coca-Prados, 1997, 1999). Production and receptors for neurotensin (Ortego and Coca-Prados, 1997), galanin (Ortego and Coca-Prados, 1998), natriuretics peptides (Ortega and Coca-Prados, 1999;Fernandez-Durango et al, 1995), angiotensin II (Cullinane et al, 2002) and endothelins (Fernandez-Durango et al, 2003) have been identified in the pigmented and nonpigmented ciliary epithelium and in cells of the trabecular meshwork (Escribano and Coca-Prados, 2002). Having shown that ghrelin's mRNA is present in the posterior ephitelium of the iris and in the non-pigmented epithelium of the ciliary body the present study indicates that ghrelin possibly is also a product of that ''neuroendocrine gland''.…”

Na+/H+ and Cl–/HCO3 –-antiporters of bovine pigmented ciliary epithelial cells

“…The amount of starting RNA was less than usual to avoid the melanin-associated inhibition of in vitro cDNA formation obtained with RNA extracted from the ciliary body [36]. The high PCR cycle number was chosen both to compensate for reduced input RNA, and to maximize sensitivity of detection.…”

Molecular Evidence That Human Ocular Ciliary Epithelium Expresses Components Involved in Phototransduction

“…Many of the neuroendocrine peptides and hormones synthesized by the NPE cells are released and found in the aqueous humor with their neuropeptide-processing enzymes (5). Among the regulatory peptides identified figured neurotensin and natriuretic peptides, and the precursor of angiotensin, angiotensinogen, which are all known to modulate blood pressure in the cardiovascular system (7).…”