The Ciliary Body - The Third Organ Found to Synthesize Indoleamines in Humans

Abstract

Indoleamines are associated with circadian rhythms in pineal gland and retina. Because the ciliary epithelium has an embryonic origin similar to that of pineal gland and retina, and intraocular pressure shows circadian variations, indoleamines were searched for in aqueous humor and ciliary body in humans. In aqueous humor, serotonin, 6-hydroxymelatonin, and melatonin were simultaneously detected and measured using high-performance liquid chromatography with electrochemical detection. The concentration was 48.7 +/- 10.9 ng/ml for serotonin, 0.47 +/- 0.8 ng/ml for melatonin, and 13.9 +/- 7.7 ng/ml for 6 hydroxymelatonin. In ciliary bodies from freshly enucleated human eyes, tryptophan, 5-hydroxytryptophan, serotonin, and 5-hydroxyindoleacetic acid were detected using high-performance liquid chromatography with simultaneous fluorescence- and electrochemical detection. Finally, the enzymatic activities of arylalkylamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), enzymes indispensable in the synthesis of melatonin, were measured. The NAT activity was 273 +/- 25 pmol/mg protein/hour and that of HIOMT, 13520 +/- 50 pmol/mg protein/hour in ciliary body. Comparison of these activities (NAT versus HIOMT) permits the suggestion that NAT is a limiting enzyme in serotonin metabolism in this tissue. These findings indicate that a circadian rhythm of indoleamines exists in human aqueous humor and that the human ciliary body is the third organ, after the pineal gland and the retina, found to synthesize indoleamines in humans.

Melatonin Receptors Trigger cAMP Production and Inhibit Chloride Movements in Nonpigmented Ciliary Epithelial Cells

“…This gland is not exclusively responsible for melatonin production. In the orbital cavity and in the eye, for instance, some areas, such as the retina (Cardinali and Rosner, 1971a,b;, ciliary body (Martin et al, 1992;, and harderian glands (Djeridane et al, 1998;, have the ability to synthesize and release melatonin. As occurs in other tissues, the eye melatonin exerts many of its actions by means of membrane receptors termed melatonin receptors, divided into MT 1 , MT 2 , and the putative MT 3 melatonin receptors (AlarmaEstrany and Dubocovich et al, 2010).…”

Metabolism of Melatonin by Human Cytochromes P450

“…However, MEL is present in many tis-sues that are not endowed with the full complement of hepatic cytochromes P450 (P450s); thus, tissue levels may not necessarily be a function of rates of hepatic metabolism or even directly related to plasma concentrations (Reiter and Tan, 2003). MEL is synthesized in the pineal gland, the retina, and the ciliary body (Martin et al, 1992) during the dark cycle, whereby it conveys its chronobiologic properties. Evidence is accumulating that many other tissues, for example, gastrointestinal and skin cells, may have the ability to synthesize MEL (Reiter and Tan, 2003).…”

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT1A and 5-HT2 Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

“…Furthermore, the selective 5-HT 2 receptor agonist R-(Ϫ)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane lowered intraocular pressure in the primate model, demonstrating a pharmacological response associated with activation of the 5-HT 2 receptor. These observations suggest that compounds that function as efficient agonists at 5-HT 2 receptors should be considered as potential agents for the control of intraocular pressure in the treatment of ocular hypertension and glaucoma in humans.Identification of several of the numerous serotonin receptors in ocular tissues of the anterior segment of the eye, including the iris-ciliary body of rabbit (Chidlow et al, 1998) and human (Martin et al, 1992), suggests that this neurotransmitter may play an important role in the regulation of intraocular pressure (IOP). Serotonin (5-hydroxytryptamine; 5-HT) is also found in the aqueous humor of humans (Veglio et al, 1998) and other mammals (Boerrigter et al, 1992).…”

“…Identification of several of the numerous serotonin receptors in ocular tissues of the anterior segment of the eye, including the iris-ciliary body of rabbit (Chidlow et al, 1998) and human (Martin et al, 1992), suggests that this neurotransmitter may play an important role in the regulation of intraocular pressure (IOP). Serotonin (5-hydroxytryptamine; 5-HT) is also found in the aqueous humor of humans (Veglio et al, 1998) and other mammals (Boerrigter et al, 1992).…”