Effects of antiglaucoma drugs on collagen gel contraction mediated by human corneal fibroblasts.
OBJECTIVE
Measurement of intraocular pressure is affected by the shape and thickness of the cornea, and corneal shape is thought to be maintained by contraction of corneal fibroblasts. The effects of the antiglaucoma drugs latanoprost, timolol maleate, and pilocarpine on the contraction of corneal fibroblasts cultured in a 3-dimensional collagen gel were investigated. The effects of these drugs on collagen degradation by corneal fibroblasts and their possible cytotoxicity were also examined.


METHODS
Human corneal fibroblasts were cultured in a 3-dimensional gel of type I collagen and in the presence of various concentrations of latanoprost, timolol maleate, or pilocarpine for various times. Collagen gel contraction was evaluated by daily measurement of gel diameter. The extent of collagen degradation was determined by measurement of the amount of hydroxyproline generated by acid-heat hydrolysis of culture supernatants. The release of lactate dehydrogenase from corneal fibroblasts was determined as an index of drug cytotoxicity.


RESULTS
Latanoprost stimulated collagen gel contraction mediated by corneal fibroblasts in a concentration- and time-dependent manner, whereas timolol maleate and pilocarpine had no such effect. None of the 3 drugs affected collagen degradation by corneal fibroblasts or exhibited cytotoxicity at concentrations as high as 100 muM.


CONCLUSIONS
Among the antiglaucoma drugs examined, only latanoprost stimulated collagen gel contraction mediated by human corneal fibroblasts. This action of latanoprost might affect corneal shape and thereby influence measurement of intraocular pressure.
Liu
Yang
Y
Department of Biomolecular Recognition and Ophthalmology, Yamaguchi University School of Medicine, Ube City, Yamaguchi, Japan.
Yanai
Ryoji
R
Lu
Ying
Y
Hirano
Shinji
S
Sagara
Takeshi
T
Nishida
Teruo
T
D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000187:drug effects*; D003286:Contracture / Q000139:chemically induced; D003319:Corneal Stroma / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D005782:Gels; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D010862:Pilocarpine / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
D000959:Antihypertensive Agents; D024042:Collagen Type I; D005782:Gels; D011461:Prostaglandins F, Synthetic; D014746:Vimentin; D010862:Pilocarpine; D000077338:Latanoprost; D013999:Timolol; D007770:L-Lactate Dehydrogenase; D006909:Hydroxyproline