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L. M. Hodgkinson, G. Duncan, L. Wang, D. Edwards; Differential Gene Expression of the MMPs and TIMPs in the Adult Human Lens Capsular Bag After Cataract. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5644.
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© ARVO (1962-2015); The Authors (2016-present)
The principle focus of this research was to study gene expression in lens proliferative events following cataract surgery. Matrix Metalloproteinases (MMPs) and the Tissue Inhibitors of the MMPs (TIMPs) have been implicated in lens growth, remodeling and the epithelial-mesenchymal transition. The expression of these genes was therefore investigated in adult human lens capsular bags which contained intraocular lenses following cataract surgery.
Human eye globes which had been donated for research were obtained <24 hours postmortem. Control group capsular bags were prepared by carrying out a sham cataract operation (55-77 yr) prior to the dissection of the lens capsular bag. Eye globes containing intraocular lenses (IOLs) (n=10 from 6 donors, 70-81 yrs) were dissected out and had the IOL removed. All were snap frozen in liquid nitrogen. Quantitative Real time reverse transcription PCR was used to analyze gene expression relative to 18S ribosomal RNA endogenous control.
Generally, normal capsular bags show low MMP and high TIMP gene expression, except for the membrane type MT1 and MT2-MMP (MMP-14, -15), which are highest in anterior epithelium and fibers respectively (reported, ARVO 2006). In comparison, human lens capsular bags, following surgical intervention for cataract, showed an up regulated expression of all MMP and TIMP genes. This included the gelatinases MMP-2 and -9 and the majority of the MT-MMPs. The gene expression of both MT1-MMP and TIMP-2 were however significantly down regulated. The extracellular matrix component fibronectin and cytoskeletal component α-smooth muscle actin were also up regulated in capsular bag samples with IOLs.
In normal human lens MMP activity is under very tight control. However remodeling and growth involves a general up regulation of the majority MMPs and TIMPs, including the gelatinases. The striking down regulation of MT1-MMP and TIMP-2 suggests that these proteins play major roles in maintaining epithelial function. It is therefore highly significant that the gene expression of these proteins is decreased in proliferative events following cataract surgery. Gene up regulation of structural components are characteristic of the myofibroblastic phenotype.
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