Prota G, Vincensi M R, Napolitano A, Selen G, Stjernschantz J
Department of Organic and Biological Chemistry, University of Naples Federico II, Italy.
Pigment Cell Res. 2000 Jun;13(3):147-50. doi: 10.1034/j.1600-0749.2000.130305.x.
Latanoprost, the active principle of Xalatan eye drops, is a prostaglandin F2alpha analogue in widespread use for the treatment of glaucoma. During chronic treatment with the drug, an increased pigmentation of the iris was observed in both primates and man. To gain an insight into the nature of this effect, we analyzed the stroma of the irides of cynomolgus monkeys subjected to 25-38 weeks of treatment. A highly sensitive procedure, based on chemical degradation by alkaline hydrogen peroxide oxidation, or hydriodic acid hydrolysis, was developed, which allowed eumelanin and pheomelanin analysis of a single iris at a time. Untreated monkey irides were found to be essentially pheomelanic, providing further support to the recently reported occurrence of these pigments in human irides. In the Latanoprost-treated eyes, the amount of eumelanin increased from three to sevenfold, while the variation of pheomelanin did not exceed 25%. The increase in eumelanin/pheomelanin ratio in the treated eyes, as compared with the contralateral control eyes, varied from three to fivefold, and the change was statistically significant (P < 0.01; t-test). Based on the results of parallel studies, showing that Latanoprost does not induce proliferation of iridial melanocytes, and that the other pigmented layers of the iris which do not contain melanocytes are not affected by the drug, it can be concluded that the observed effect is a result of a direct interaction with the melanogenic mechanism. This probably involves activation of tyrosinase, as suggested, to account for the stimulation of melanin synthesis by related compounds, including natural prostaglandins.
拉坦前列素是适利达滴眼液的活性成分，是一种广泛用于治疗青光眼的前列腺素F2α类似物。在使用该药物的长期治疗过程中，在灵长类动物和人类中均观察到虹膜色素沉着增加。为深入了解这种效应的本质，我们分析了接受25 - 38周治疗的食蟹猴虹膜基质。我们开发了一种基于碱性过氧化氢氧化化学降解或氢碘酸水解的高灵敏度方法，该方法可一次对单个虹膜进行真黑素和褐黑素分析。未治疗的猴虹膜主要含褐黑素，这进一步支持了最近报道的这些色素在人类虹膜中的存在情况。在接受拉坦前列素治疗的眼睛中，真黑素的量增加了三到七倍，而褐黑素的变化不超过25%。与对侧对照眼相比，治疗眼的真黑素/褐黑素比值增加了三到五倍，且变化具有统计学意义（P < 0.01；t检验）。基于平行研究的结果，表明拉坦前列素不会诱导虹膜黑素细胞增殖，且虹膜中不含黑素细胞的其他色素层不受该药物影响，可以得出结论，观察到的效应是与黑素生成机制直接相互作用的结果。如前所述，这可能涉及酪氨酸酶的激活，以解释包括天然前列腺素在内的相关化合物对黑素合成的刺激作用。
