Identification of a neuropeptide and neuropeptide-processing enzymes in aqueous humor confers neuroendocrine features to the human ocular ciliary epithelium.
The ocular ciliary epithelium, the site of aqueous humor secretion in the mammalian eye, is believed to play a key function in signaling mechanisms that regulate the rate of secretion, and thus intraocular pressure. One possible way of mediating these signaling functions is through neuropeptides and hormones secreted into the aqueous humor and acting on target tissues. We recently identified a cDNA clone sharing 100% identity with carboxypeptidase E (CPE), a neuropeptide-processing enzyme. Utilizing polymerase chain reaction, we further identified and characterized another processing enzyme, the peptidylglycine alpha-amidating monooxygenase (PAM), and the neuropeptide secretogranin II, a molecular marker restricted to neuroendocrine tissues. Using specific probes, we found that the nonpigmented ciliary epithelial cells express CPE, PAM, and secretogranin II mRNA, and protein. We also found that CPE and secretogranin II are abundant in aqueous humor. Treatment of cultured ciliary epithelial cells with veratridine and phorbol ester up-regulates CPE and PAM. Secretogranin II was found to be induced by veratridine, whereas phorbol ester had little effect, suggesting different mechanisms for secretion. The results demonstrate that secretogranin II, CPE, and PAM represent a specialized group of neuropeptide and neuropeptide-processing enzymes secreted by the ciliary epithelial cells which may confer to them neuroendocrine functions in cell-cell communication or cell signaling.
Ortego
J
J
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Escribano
J
J
Crabb
J
J
Coca-Prados
M
M
D000328:Adult; D000368:Aged; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001483:Base Sequence; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000378:metabolism*; D002460:Cell Line; D002675:Child, Preschool; D002864:Chromogranins; D002924:Ciliary Body / Q000166:cytology / Q000502:physiology*; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009490:Neurosecretory Systems / Q000502:physiology*; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D051381:Rats
D002864:Chromogranins; D009097:Multienzyme Complexes; D011506:Proteins; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D002268:Carboxypeptidases; D043423:Carboxypeptidase H