Effect of latanoprost on the extracellular matrix of the ciliary muscle. A study on cultured cells and tissue sections.
Prostaglandin F2alpha and its analogue latanoprost, both prostanoid FP receptor agonists, reduce the intraocular pressure mainly by enhancing uveoscleral outflow. Changes in the extracellular matrix of the ciliary muscle may be involved in the increased outflow. The effect of latanoprost and prostaglandin F2alpha on the extracellular matrix of the ciliary muscle was investigated. Cell cultures of human ciliary muscle were treated with latanoprost acid or prostaglandin F2alpha for 1-2 days and were immunostained against various extracellular matrix components and metalloproteinases. Proteinases were also analysed by zymography and by measuring plasmin generating ability. For comparison, matrix components were immunolocalized on tissue sections from monkey eyes, treated topically once daily with latanoprost for 10 days. In response to both prostaglandins collagens I, III, and IV, fibronectin, laminin and hyaluronan were reduced, while metalloproteinase -2 and -3 were increased. Zymography demonstrated the presence of functionally active metalloproteinase -2. Both prostaglandins enhanced the generation of plasmin, an activator of metalloproteinases. In the anterior part of the ciliary muscle in latanoprost-treated eyes immunostained collagen VI was decreased in 5 out of 5 monkeys and collagen IV was decreased in 4 of the 5 monkeys. These results suggest a role for latanoprost in the remodeling of extracellular matrix in the ciliary muscle. A latanoprost-induced change in the extracellular matrix might augment the flow of aqueous humour through the ciliary muscle bundles of the uveoscleral pathway.
Ocklind
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Glaucoma Research Laboratories, Pharmacia & Upjohn AB (publ), Uppsala, S-751 82, Sweden.
D000368:Aged; D000818:Animals; D018929:Cell Culture Techniques; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005341:Fibrinolysin / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D000077338:Latanoprost; D008252:Macaca fascicularis; D008666:Metalloendopeptidases / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D003094:Collagen; D005341:Fibrinolysin; D008666:Metalloendopeptidases