Differential gene expression in the human ciliary epithelium

The generation of expression and subtractive libraries from the ocular cili ary body and cultured ciliary epithelial cells has been instrumental in the cloning, identification and characterization of many gene which, overall r eflect a representative profile of transcripts expressed in ciliary nonpigm ented, ciliary pigmented and ciliary muscle cells. The cell-specific expres sion of some of these genes (i.e. a neurotrophic factor, a gene associated with juvenile open glaucoma, and a visual component) reveal a degree of cel l differentiation with a diversity of functions and properties higher than previously thought. The protection from light-induced oxidative reactions, free radicals and detoxification, may be partially attributed to the high l evel of expression in the ciliary epithelium of antioxidative enzymes (i.e. , glutathione S-transferase, glutathione peroxidases, selenoprotein-P). The expression of genes encoding plasma proteins (i.e. complement component C4 , alpha 2-macroglobulin apolipoprotein D) is in contrast with the view that plasma proteins in aqueous humor are synthesized outside the eye (i.e., li ver). The identification of neuropeptide-processing enzymes (i.e. prohormon e convertases, carboxypeptidase E, peptidyl-glycine-alpha-amidating monoxig enase), neuropeptides (i.e., secretorgranin II, neurotensin) and regulatory peptides (i.e., atrial natriuretic peptide and angiotensinogen) with hyper tensive and hypotensive activities provide the molecular basis to support t he view that the ciliary epithelium is a neuroepithelium with neuroendocrin e functions. We propose a working model to demonstrate that aqueous humor a nd intraocular pressure are under neuroendocrine control through regulatory peptides synthesized and released by the ciliary epithelium and targeting the peptide producing cells at the inflow system by an autocrine mechanism and or cells at the outflow system (i.e., trabecular meshwork cells) by a p aracrine mechanism. Finally, we hypothesize that these mechanisms could be entrained in the light dark cycle following the circadian rhythm of aqueous humor and intraocular pressure. (C) 1999 Elsevier Science Ltd. All rights reserved.