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Editors Selection IGR 9-3

Medical treatment: MMP

Comment by James Lindsey on:

13529 Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost, Oh DJ; Martin JL; Williams AJ et al., Investigative Ophthalmology and Visual Science, 2006; 47: 953-963

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Intraocular pressure reduction following topical treatment with latanoprost has been linked with increased ciliary muscle expression of four types of human matrix metalloproteinases (MMPs), and two types of tissue inhibitors of matrix metalloproteinases (TIMPs). To further investigate this response, Oh et al. (35) assessed the expression of 13 MMP mRNAs and 4 TIMP mRNAs in the ciliary muscle of post-mortem human ciliary muscle. They also looked for induction of these mRNAs in cultured ciliary smooth muscle cells exposed to latanoprost acid. Their PCR experiments were well designed, with appropriate controls. However, there was no mention of exclusion factors for the analyzed donor eye tissue such as the presence or history of systemic or ocular disease. Although message for most of the MMPs and for all of the TIMPs was detected, consistent increases in response to physiological latanopost doses were only observed for MMP-3, MMP-17, and TIMP-3.

An important limitation noted by the authors is that mRNA changes were only assessed 24 hours after adding latanoprost to the cultures. Hence, increases in MMP or TIMP mRNA that subsided prior to 24 hours, such as occurs with MMP-1, were missed. Also, this study did not address MMP activation or inactivation, which occur extracellularly. Finally, only 13 of the 21 known human MMP genes were studied.

This study makes two important contributions. Firstly, because MMP-17 can activate aggrecanase-1, its induction with latanoprost results raises the possibility that degradation of proteoglycans may accompany degradation of collagens. Secondly, these results support the view that variable inductions for many MMP types may contribute to the variable IOP reductions observed among different patients receiving latanoprost.

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