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.
Calcium-channel blockers have long been employed in coronary disease, and recent investigations have indicated their efficacy in improving the visual field in low-tension glaucoma or presumed vasospasm, possibly by enhancing ocular circulation. We evaluated the short-term influence of a typical calcium-channel blocker, nifedipine, on 59 patients with visual-field defects, some with optic-nerve-head pathology (n = 38) and some with normal-appearing optic nerve heads (n = 21). On the average, a statistically significant improvement of 1.2 dB was observed. Different types of patients, however, behaved quite differently. The younger the patient, the greater the improvement. Patients with normal optic nerve heads improved by 1.54 dB, whereas patients with optic-nerve-head excavation improved by only 0.66 dB. No response was observed in patients with anterior ischemic neuropathy. Marked deterioration was noted in one glaucoma patient with low systemic blood pressure. The visual-field changes were observed in the scotomatous and non-scotomatous areas. Thus, the calcium-channel blocker nifedipine can be effective in some selected diseases whose pathogenesis probably involves vascular dysregulation though it may even be contraindicated in others.
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