Lindquist N G, Larsson B S, Stjernschantz J
Department of Pharmaceutical Biosciences, Division of Toxicology, BMC, Uppsala University, Uppsala, S-751 24, Sweden.
Exp Eye Res. 1999 Oct;69(4):431-6. doi: 10.1006/exer.1999.0718.
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.
哺乳动物眼中的黑素细胞一直被认为仅在胎儿发育期间以及非常年幼的个体中产生黑色素。最近的一项发现表明，用于治疗青光眼的前列腺素类似物拉坦前列素会导致猴子和人类的虹膜色素沉着增加，这表明虹膜黑素细胞在成年个体中也能产生黑色素。在早期的一项研究中，我们使用HG-（3）H-甲巯咪唑（一种假黑色素前体）的微放射自显影技术，观察到成年小鼠的虹膜黑素细胞和虹膜色素上皮中似乎存在持续的黑色素生成。在本研究中，将拉坦前列素（13,14-二氢-17-苯基-18,19,20-三降-PGF（2α）-异丙酯）每日一次应用于七只食蟹猴的右眼；左眼作为未治疗的对照。在治疗的前三个月中，有两只动物的治疗眼出现了明显的虹膜色素沉着增加。给这些动物静脉注射G-（3）H-甲巯咪唑，并在注射后24小时处死。取出眼睛，固定在补充有10%乙酸的4%福尔马林中，然后包埋在石蜡或Polybed 812中。眼睛的切片用于微放射自显影和光学显微镜检查。在未治疗眼的虹膜中的一些黑素细胞中观察到放射性的高摄取。在睫状体基质和脉络膜的黑素细胞中也有低摄取。在虹膜或视网膜色素上皮中未观察到积累。在治疗眼的虹膜中，与未治疗眼唯一观察到的差异是虹膜黑素细胞中的黑色素量增加，并且大量这些细胞中的放射性摄取增加。因此，在某些个体中用拉坦前列素治疗似乎会导致虹膜黑素细胞中正常黑色素合成的低水平增加。
