EFFECT OF LATANOPROST ON THE EXTRACELLULAR-MATRIX OF THE CILIARY MUSCLE - A STUDY ON CULTURED-CELLS AND TISSUE-SECTIONS

Prostaglandin F-2 alpha and its analogue latanoprost, both prostanoid FP receptor agonists, reduce the intraocular pressure mainly by enhanc ing uveoscleral outflow. Changes in the extracellular matrix of the ci liary muscle may be involved in the increased outflow, The effect of l atanoprost and prostaglandin F-2 alpha on the extracellular matrix of the ciliary muscle was investigated. Cell cultures of human ciliary mu scle were treated with latanoprost acid or prostaglandin F-2 alpha for 1-2 days and were immunostained against various extracellular matrix components and metalloproteinases, Proteinases were also analysed by z ymography 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 r esponse to both prostaglandins collagens I, IIII 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 generati on of plasmin, an activator of metalloproteinases. In the anterior par t of the ciliary muscle in latanoprost-treated eyes immunostained coll agen VI was decreased in 5 out of 5 monkeys and collagen IV was decrea sed in 4 of the 5 monkeys. These results suggest a role for latanopros t in the remodeling of extracellular matrix in the ciliary muscle. A l atanoprost-induced change in the extracellular matrix might augment th e flow of aqueous humour through the ciliary muscle bundles of the uve oscleral pathway. (C) 1998 Academic Press.