Increased pigmentation of iridial melanocytes in primates induced by a prostaglandin analogue.
The melanocytes in the mammalian eye have been thought to produce melanin only during fetal development and in the very young individual. The recent discovery that latanoprost, a prostaglandin analogue used in the treatment of glaucoma, causes increased pigmentation of the iris in monkeys and in humans indicates that the iridial melanocytes can produce melanin in adult individuals. Using microautoradiography of HG-(3)H-methimazole, a false melanin precursor, we observed in an earlier study that there seems to be an ongoing melanogenesis in adult mice in the iridial melanocytes and in the iridial pigment epithelium. In the present study latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-PGF(2alpha)-isoprop yl ester) was applied once daily to the right eye of seven cynomolgus monkeys; the left eye served as an untreated control. Two animals developed clear-cut increased pigmentation of the iris in the treated eye during the first three months of treatment. These animals were injected intravenously with G-(3)H-methimazole and were killed 24 hr after the injection. The eyes were removed, fixed in 4% formalin supplemented with 10% acetic acid and embedded in paraffin or Polybed 812. Sections from the eyes were used for microautoradiography and light microscopic examination. A high uptake of radioactivity was observed in a few melanocytes in the iris of the untreated eye. There were also a low uptake in the melanocytes in the stroma of the ciliary body and the choroid. No accumulation was observed in the iridial or retinal pigment epithelium. In the iris of the treated eye the only observed difference from the untreated eye was an increased amount of melanin in the iridial melanocytes and an increased uptake of radioactivity in a great number of these cells. Thus it seems likely that treatment with latanoprost in some individuals causes an increase of the low normal melanin synthesis in iridal melanocytes.
Lindquist
N G
NG
Department of Pharmaceutical Biosciences, Division of Toxicology, BMC, Uppsala University, Uppsala, S-751 24, Sweden.
Larsson
B S
BS
Stjernschantz
J
J
D000818:Animals; D005127:Eye Color / Q000187:drug effects*; D005260:Female; D007498:Iris / Q000187:drug effects / Q000378:metabolism*; D000077338:Latanoprost; D008252:Macaca fascicularis; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D008713:Methimazole; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*
D008543:Melanins; D011461:Prostaglandins F, Synthetic; D008713:Methimazole; D000077338:Latanoprost