Archives of ophthalmology (Chicago, Ill. : 1960) · 2010
Effect of latanoprost on the expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 on the ocular surface.
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Honda Norihiko, Miyai Takashi, Nejima Ryohei, Miyata Kazunori, Mimura Tatsuya, Usui Tomohiko, Aihara Makoto, Araie Makoto, Amano Shiro
Аннотация
OBJECTIVE: To investigate the effect of topical latanoprost on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase 1 (TIMP-1) on the ocular surface.
METHODS: Tears were collected from 39 patients with glaucoma who used latanoprost, 0.005%, eyedrops (Xalatan) and 28 healthy volunteers. The MMP-9 concentration was measured. Conjunctival epithelial cells were collected from 10 eyes of 10 patients before and 1 to 3 months after starting to take topical latanoprost, 0.005%, and MMP-1, MMP-9, and TIMP-1 messenger RNA (mRNA) expression was analyzed. Both eyes of 48 mice were treated once a day with latanoprost, 0.005%, timolol gel, 0.5%, eyedrops, vehicle of Xalatan, or phosphate-buffered saline, and MMP-9 and TIMP-1 mRNA expression was analyzed.
RESULTS: The median MMP-9 concentration in latanoprost-treated cases was 91.2 ng/mL (in controls, 19.7 ng/mL; P < .001). In latanoprost-treated cases, the relative ratio of MMP-9 to glyceraldehyde 3-phosphate dehydrogenase mRNA was significantly increased from 6.42 to 21.3 (P = .04, paired t test) and the relative amount of TIMP-1 was significantly decreased from 154 to 105 (P = .009). The relative amount of MMP-1 to GAPDH mRNA before and after latanoprost use was not significantly different (P = .16). In mice, MMP-9 expression was increased and TIMP-1 expression was decreased on the ocular surface at 8 weeks after latanoprost use.
CONCLUSION: The topical use of latanoprost increases MMP-1 and MMP-9 and decreases TIMP-1 on the ocular surface.
CLINICAL RELEVANCE: The use of topical latanoprost might not be recommended in patients with keratoconus or after laser-assisted in situ keratomileusis.
METHODS: Tears were collected from 39 patients with glaucoma who used latanoprost, 0.005%, eyedrops (Xalatan) and 28 healthy volunteers. The MMP-9 concentration was measured. Conjunctival epithelial cells were collected from 10 eyes of 10 patients before and 1 to 3 months after starting to take topical latanoprost, 0.005%, and MMP-1, MMP-9, and TIMP-1 messenger RNA (mRNA) expression was analyzed. Both eyes of 48 mice were treated once a day with latanoprost, 0.005%, timolol gel, 0.5%, eyedrops, vehicle of Xalatan, or phosphate-buffered saline, and MMP-9 and TIMP-1 mRNA expression was analyzed.
RESULTS: The median MMP-9 concentration in latanoprost-treated cases was 91.2 ng/mL (in controls, 19.7 ng/mL; P < .001). In latanoprost-treated cases, the relative ratio of MMP-9 to glyceraldehyde 3-phosphate dehydrogenase mRNA was significantly increased from 6.42 to 21.3 (P = .04, paired t test) and the relative amount of TIMP-1 was significantly decreased from 154 to 105 (P = .009). The relative amount of MMP-1 to GAPDH mRNA before and after latanoprost use was not significantly different (P = .16). In mice, MMP-9 expression was increased and TIMP-1 expression was decreased on the ocular surface at 8 weeks after latanoprost use.
CONCLUSION: The topical use of latanoprost increases MMP-1 and MMP-9 and decreases TIMP-1 on the ocular surface.
CLINICAL RELEVANCE: The use of topical latanoprost might not be recommended in patients with keratoconus or after laser-assisted in situ keratomileusis.
Предметные рубрики MeSH
Administration, TopicalAnimalsAntihypertensive AgentsBlotting, WesternConjunctivaEnzyme-Linked Immunosorbent AssayEpithelial CellsFemaleGlaucoma, Open-AngleGlyceraldehyde 3-Phosphate Dehydrogenase (NADP+)HumansImmunohistochemistryIntraocular PressureLatanoprostLow Tension GlaucomaMaleMatrix Metalloproteinase 1Matrix Metalloproteinase 9MiceMiddle AgedProstaglandins F, SyntheticRNA, MessengerReverse Transcriptase Polymerase Chain ReactionTearsTissue Inhibitor of Metalloproteinase-1