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L.M. Hodgkinson, G. Duncan, L. Wang, D. Edwards, C. Pennington; Differential Gene Expression of the Matrix Metalloproteinases (MMPs) and Their Inhibitors the Tissue Inhibitors of the Matrix Metalloproteinases (TIMPs) in the Human Lens . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2559.
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© ARVO (1962-2015); The Authors (2016-present)
Matrix Metalloproteinases (MMPs) and their inhibitors, the Tissue Inhibitors of Matrix Metalloproteinases (TIMPs), have been implicated in lens growth, development and remodelling. The gene expression of the MMP and TIMP families was therefore investigated in regions of the normal adult human lens using quantitative Real Time RT–PCR.
Normal adult human globes (n=12, age range 55–77 years) were obtained < 24 hours postmortem and the lenses dissected into three regions; anterior epithelium, equatorial region and fibres. Primary cultures generated from anterior epithelial cells were investigated as a growth and remodelling system. Total RNA was extracted from tissue that had been snap–frozen in liquid nitrogen and maintained for a short time at –80ºC. Gene expression was normalised relative to18S ribosomal RNA endogenous control.
Absent or low levels of MMP gene expression were determined in the three lens regions, except for the membrane type (MT–) MT1–MMP (MMP–14) and MT2–MMP (MMP–15). There was low expression of Gelatinase A (MMP–2) and negligible Gelatinase B (MMP–9). Generally, regional MMP expression levels occurred in the order of anterior cells>equator>fibre. However, while MT1–MMP expression declined from anterior to fibres, MT2–MMP expression increased. Relatively high levels of the four inhibitory TIMPs were maintained throughout. A different picture emerges with the primary cultures. Gene upregulation of several MMP groups occurred including the Gelatinases and the Stromelysins: MMP–3, –10 and –11. Of the Collagenases, MMP–1 was high but –8 and –13 were absent. MMP–19 and MT5–MMP (MMP–24) were also elevated. An upregulation of TIMP–1 gene expression occurred in culture but TIMP–4 appeared to be decreased.
In normal aged human lens cells MMP activity is under very tight control with a general low expression of the MMPs and high expression of the TIMPs. Normal differentiation was generally associated with a decline in expression of the MMPs, which was particularly marked for MT1–MMP. Conversely MT2–MMP expression increased significantly. Remodelling and growth involved a general upregulation of the MMPs.
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