Effect of latanoprost on the expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 on the ocular surface.
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.


CONCLUSIONS
The topical use of latanoprost increases MMP-1 and MMP-9 and decreases TIMP-1 on the ocular surface.


CONCLUSIONS
The use of topical latanoprost might not be recommended in patients with keratoconus or after laser-assisted in situ keratomileusis.
Honda
Norihiko
N
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
Miyai
Takashi
T
Nejima
Ryohei
R
Miyata
Kazunori
K
Mimura
Tatsuya
T
Usui
Tomohiko
T
Aihara
Makoto
M
Araie
Makoto
M
Amano
Shiro
S
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D003228:Conjunctiva / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy / Q000201:enzymology; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D057066:Low Tension Glaucoma / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013666:Tears / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D000077338:Latanoprost; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1