Abstract
Purpose: :
Topical prostaglandins, which signal through the prostaglandin (PG) FP receptor, lower intraocular pressure (IOP) in monkeys. Treatment is associated with an upregulation of matrix metalloproteinases (MMPs). We have previously demonstrated that single applications of topical prostaglandins reduce IOP in the mouse, but the effect of treatment on MMP expression is not known. The current study was undertaken to determine the distribution of MMP expression in the mouse eye and to determine whether MMPs are upregulated by topical prostaglandins.
Methods: :
The right eyes of Swiss White mice were treated daily for seven days with topical latanoprost, while the fellow eyes were treated with a vehicle control. MMP 2 and 9 expression was investigated at the protein level by immunohistochemistry (n=5). Fluorescence intensity was quantified from digital photographs using image analysis software. MMP 2 and 9 expression at the gene level was determined by real–time PCR in uvea, retina, and sclera from pooled tissue of treated and untreated eyes (n=12).
Results: :
Constitutive MMP 2 expression is widespread in the ocular tissues of the mouse eye, while MMP 9 expression is generally weaker than that of MMP 2. Treatment with latanoprost had no significant effect on MMP 2 and MMP 9 expression at the protein level. At the RNA level, however, treatment with latanoprost yielded significant upregulation of MMP 2 and MMP 9 mRNA. For MMP 2, there is a 1.28 fold increase in the sclera, 1.11 fold increase in the retina, and a 3.56 fold increase in the uvea, while for MMP 9, there is a 2.22 fold increase in the sclera, a 1.09 fold increase in the retina, and a 1.16 fold increase in the uvea.
Conclusions: :
MMP 2 and MMP 9 are expressed constitutively in the mouse eye. We did not detect significant upregulation by immunohistochemistry after seven days of treatment with topical latanoprost. However, treatment resulted in an increase in MMP 2 and MMP 9 mRNA.
Keywords: pharmacology • outflow: ciliary muscle • microscopy: light/fluorescence/immunohistochemistry