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J. G. Crowston, J. D. Lindsey, M. Angert, Q. Liu, W.-K. Ju, R. N. Weinreb; The Role of the FP Receptor in Prostaglandin-Mediated MMP Upregulation in the Mouse Eye. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1551.
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Prostaglandin FP receptor agonists lower intraocular and have been shown to upregulate MMP expression in many tissue culture models. Equivalent data from in-vivo models is limited and the role of the FP receptor in MMP upregulation is not known. This study determined the effect of topical prostaglandin on MMP expression in the normal mouse eye and evaluated the role of the prostaglandin FP receptor on MMP gene expression using FP receptor knockout mice.
To determine change in MMP expression over time, wildtype mice were treated once daily with topical latanoprost (200ng). Sclera and retina (n=5 per time point) were harvested after 2-hours, 1,3 and 7-days of treatment and pooled MMP mRNA was quantified by real-time PCR and compared to untreated control eyes. To assess the role of the FP receptor, FP knockout and wildtype littermate controls were treated daily for 7 days and MMP expression was determined in sclera and retina and compared to untreated fellow eyes. A further control group (n=4) received benzylkonium chloride (0.02%) daily for seven days. A 30% change in gene expression was defined as being of physiological significance.
MMP-2, MMP-3, MMP-9 and FP mRNA was upregulated in sclera with peak expression at day 7. These genes were not upregulated in retina at any time point. In FP receptor knockout mice there was no increase in MMP gene expression in sclera compared to untreated fellow eyes. Significant increases in MMP gene expression were observed in the wildtype littermates with intact FP receptors (Table 1). Benzylkonium chloride did not increase MMP gene expression in sclera or retina compared to untreated controls.
Topical latanoprost upregulates MMP- 2,MMP-3, MMP-9 and FP receptor gene expression in mouse sclera. These responses are critically dependant on an intact FP receptor gene.
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