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 mec hanisms that regulate the rate of secretion, and thus intraocular pres sure, One possible way of mediating these signaling functions is throu gh neuropeptides and hormones secreted into the aqueous humor and acti ng on target tissues, We recently identified a cDNA clone sharing 100% identity with carboxypeptidase E (CPE), a neuropeptide-processing enz yme, Utilizing polymerase chain reaction, we further identified and ch aracterized another processing enzyme, the peptidylglycine alpha-amida ting monooxygenase (PAM), and the neuropeptide secretogranin II, a mol ecular marker restricted to neuroendocrine tissues, Using specific pro bes, we found that the nonpigmented ciliary epithelial cells express C PE, PAM, and secretogranin II mRNA, and protein. We also found that CP E and secretegranin II are abundant in aqueous humor, Treatment of cul tured ciliary epithelial cells with veratridine and phorbol ester up-r egulates CPE and PAM. Secretogranin II was found to be induced by vera tridine, 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 neu ropeptide-processing enzymes secreted by the ciliary epithelial cells which may confer to them neuroendocrine functions in cell-cell communi cation or cell signaling.