ABSTRACT
The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha) receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible.
Subject(s)
Antihypertensive Agents/adverse effects , Cloprostenol/analogs & derivatives , Dinoprost/analogs & derivatives , Eye Color/drug effects , Iris Diseases/chemically induced , Iris/drug effects , Pigmentation Disorders/chemically induced , Amides , Animals , Bimatoprost , Cloprostenol/adverse effects , Dinoprost/adverse effects , Gene Expression Regulation/drug effects , Humans , Iris/metabolism , Iris Diseases/metabolism , Latanoprost , Lipids/adverse effects , Melanocytes/metabolism , Monophenol Monooxygenase/genetics , Pigmentation Disorders/metabolism , Prostaglandins F, Synthetic/adverse effects , Receptors, Prostaglandin/metabolism , Travoprost , Up-RegulationABSTRACT
Cytosolic carbonic anhydrases CAI, CAII, and CAIII from liver, and CAII, and CAIII from muscle of adult male Sprague-Dawley rats were purified to homogeneity. CAIII from liver and muscle had the same amino acid composition and were immunochemically similar. Their kinetic properties at 0 degrees C were also similar. Km(CO2) was 4 mM and kcat 3x105 s(-1). Ki was 0.4 and 0.2 M for acetazolamide and NaCl, respectively. Both CAIIIs ran as single bands on SDS-electrophoresis and high-speed centrifugation, with a mol wt of 29.3 kDa. Their hydrodynamic properties suggest that CAIII is a compact, nearly spherical molecule. It contained 0.9 M zinc per M protein. In both tissues isoelectric focusing identified neutral and acidic isoforms with pIs near 7.0 and 6.3, respectively. These forms were immunologically identical and had the same amino acid composition and mol wts. The acidic forms probably represent subspecies of CAIII in different states of oxidation. CAIII is the major soluble protein in rat liver and muscle. Its function is probably to protect proteins of these tissues from oxidation catalyzed by iron-containing degradation products of haemoglobin and myoglobin. Liver CAI and CAII and muscle CAII were identical to CAI and CAII of rat erythrocytes.
