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Ramez Haddadin, Dong-Jin Oh, Douglas Rhee; Latanoprost Lowers Intraocular Pressure in Matrix Metalloproteinase 9-null Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):789.
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Prostaglandin F2α analogues, such as latanoprost, are effective intraocular pressure (IOP) lowering agents. Our group has previously shown that latanoprost results in upregulation of various matrix metalloproteinases (MMP); however, MMP9 expression is induced from an undetected level in the human ciliary body. Therefore, we hypothesize that MMP9 is critical to the IOP lowering effect of latanoprost. Transgenic mice are commonly used as models to study molecular mechanisms, and there is significant homology between human and mouse MMP9 mRNA sequences. We studied the role of MMP9 in mice by measuring the IOP reduction with latanoprost treatment in both wild-type (WT) and MMP9-null mice.
FVB/NJ WT and MMP9-null mice were bred independently, fed ad lib, and housed under identical 12/12-hour light-dark cycles (on 7:00, off 19:00). Two-month-old WT and MMP9-null mice were anesthetized by intraperitoneal (IP) injection of a ketamine/xylazine mixture. A rebound tonometer (TonoLab) was used to take 3 IOP measurements in each eye between 4 and 7 minutes after intraperitonal injection. WT and MMP9-null mice were also treated with 4 µl of 0.005% latanoprost in the treated eye and PBS in the contralateral eye. IOPs were measured at 2 hours post-treatment.
Mean daytime IOPs of WT and MMP9-null mice were 13.6 ± 1.8 mm Hg (n=54) and 14.8 ± 2.0 mm Hg (n=48), respectively. The difference in IOPs is 8.6% (p=0.003). With latanoprost treatment, the IOP-lowering effect was 17.4 ± 8.0% (n=25) and 16.2 ± 9.5% (n=23) in WT and MMP9-null mice, respectively. The difference in IOP-lowering effect was not statistically significant (p=0.64).
MMP9-null mice have significantly higher IOPs than their WT counterparts; however, the reductions in IOPs with latanoprost administration were not different. These results are contrary to expected given that MMP9 is not expressed at baseline in human ciliary body, and is induced by latanoprost. These are important considerations when studying the role of MMP9 in mice.
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