Latanoprost‐induced increase of tyrosinase transcription in iridial melanocytes

Abstract

ABSTRACT.Purpose: Latanoprost, the active principle of Xalatan R 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 mg latanoprost once daily for 10 days. The contralateral eye received the vehicle only. Tyrosinase mRNA was visualized by in situ hybridization using radiolabelled 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 posttranslational 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.

Latanoprost and Pigmentation

“…26 Latanoprost was found to affect tyrosinase at the gene transcription level in iridial melanocytes as observed in a comparison of treated and control cynomolgus monkeys. 76 This outcome was verified using human cultured iridial melanocytes from donors not previously treated with latanoprost, and further demonstrated that latanoprost can increase tyrosinase activity both in vivo and in vitro. Transcription of the tyrosinase gene in iridial melanocytes was selectively increased in mixed-color irides (hazel) but not in melanocytes from blue or brown irides.…”

“…Transcription of the tyrosinase gene in iridial melanocytes was selectively increased in mixed-color irides (hazel) but not in melanocytes from blue or brown irides. 76 Increased expression of tyrosinase also was demonstrated in six of the 30 (20%) whole iris cultures from human donors. 75 Five of the six responders had brown eyes, and the remaining responder had hazel eyes.…”

New Fluoroprostaglandin F2.ALPHA. Derivatives with Prostanoid FP-Receptor Agonistic Activity as Potent Ocular-Hypotensive Agents

“…[10][11][12][13][14][15][16][17][18][19] The PGF 2a -derivative-induced eye colour change is most likely due to an increased amount of melanin within iris stroma melanocytes. [20][21][22] These adverse effects may be related to the stimulation of prostanoid FP receptors in the eye. 3) To judge from the accumulating findings relating to latanoprost and other PGF 2a derivatives, prostanoid FP-receptor agonists are among the most promising ocular-hypotensive agents.…”

Topikal Prostaglandin Analogları ve Hiperpigmentasyon

“…8 Çeşitli çalışmalarla prostaglandinlerin hem tirozinaz gen transkripsiyonunu arttırarak hem de direkt tirozinaz enzim aktivitesini arttırarak melanogenezi arttırdığı, bunun da muhtemelen prostanoid reseptör uyarımı yolu ile olduğu gösterilmiştir. 2,8,[17][18][19][20] Elektron mikroskopisi ile yapılan çalışmalarda immatür melanozom ya da matür melanin granüllerinin sayısında değişiklik olmadan var olan melanin granüllerinin boyutunun arttığı gösterilmiştir. 8 PGA ilişkili iris hiperpigmentasyonu çoğunlukla tedavinin bitmesine rağmen düzelme göstermez veya çok yavaş gerileme gösterir.…”