Latanoprost-induced increase of tyrosinase transcription in iridial melanocytes.
OBJECTIVE
Latanoprost, the active principle of Xalatan eye drops, has been shown to cause increased iridial pigmentation as a side-effect in some patients. The purpose of the present study was to investigate whether latanoprost affects tyrosinase, the rate limiting enzyme in melanogenesis, at the gene transcription level in the iridial melanocytes.


METHODS
Four cynomolgus monkeys were treated unilaterally with 3 or 11 microg latanoprost once daily for 10 days. The contralateral eye received the vehicle only. Tyrosinase mRNA was visualized by in situ hybridization using radio-labelled riboprobes. The transcription of tyrosinase was also studied in vitro using cultivated human iridial melanocytes. Tyrosinase RNA was quantified by Northern blotting.


RESULTS
In the monkeys transcription of tyrosinase was found to be increased in iridial melanocytes of the treated eyes compared to the control eyes. Increased transcription of tyrosinase was in addition found in the iridial pigment epithelium and in melanocytes of the anterior choroid. Latanoprost was also found to increase the transcription of tyrosinase in melanocytes isolated from at least one human eye.


CONCLUSIONS
Although the tyrosinase enzyme has to undergo complex post-translational modification to become biologically active, which we have not studied, it appears that latanoprost treatment may increase the transcription of the tyrosinase gene in some individuals, consistent with increased melanogenesis in the iridial melanocytes leading to darker eye colour.
Stjernschantz
J
J
Department of Neuroscience, Uppsala University, Sweden. Johan.Stjernschantz@neuro.uu.se
Ocklind
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Wentzel
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Lake
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Hu
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002829:Choroid / Q000187:drug effects / Q000201:enzymology; D005260:Female; D017403:In Situ Hybridization; D007498:Iris / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000077338:Latanoprost; D008252:Macaca fascicularis; D008297:Male; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology; D014442:Monophenol Monooxygenase / Q000235:genetics*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000201:enzymology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D000077338:Latanoprost; D014442:Monophenol Monooxygenase