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

Abstract

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.

• Authors: Norihiko Honda, Takashi Miyai, Ryohei Nejima, Kazunori Miyata, Tatsuya Mimura, Tomohiko Usui, Makoto Aihara, Makoto Araie, Shiro Amano
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 128 Issue 4 Pg. 466-71 (Apr 2010) ISSN: 1538-3601 [Electronic] United States
• PMID: 20385943 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Prostaglandins F, Synthetic
• RNA, Messenger
• Tissue Inhibitor of Metalloproteinase-1
• Latanoprost
• Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)
• Matrix Metalloproteinase 9
• Matrix Metalloproteinase 1

Topics

• Administration, Topical
• Animals
• Antihypertensive Agents (administration & dosage)
• Blotting, Western
• Conjunctiva (enzymology)
• Enzyme-Linked Immunosorbent Assay
• Epithelial Cells (enzymology)
• Female
• Glaucoma, Open-Angle (drug therapy, enzymology)
• Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) (genetics)
• Humans
• Immunohistochemistry
• Intraocular Pressure (drug effects)
• Latanoprost
• Low Tension Glaucoma (drug therapy, enzymology)
• Male
• Matrix Metalloproteinase 1 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Middle Aged
• Prostaglandins F, Synthetic (administration & dosage)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tears (enzymology)
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)