Induction of Matrix Metalloproteinases 2 and 9 following Stress to the Lens

Tamiya, Shigeo; Wormstone, I. Michael; Marcantonio, Julia M.; Gavrilović, Jelena; Duncan, G.

doi:10.1006/exer.2000.0916

Cited by 56 publications

(41 citation statements)

References 34 publications

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“…In the eye, excessive, inappropriate, or reduced gelB expression has been linked to improper corneal wound healing, formation of chronic corneal ulcers, cataracts, glaucoma, and proliferative retinopathies (16,37,49,52,54). It is interesting that at later developmental stages and into adulthood both Pax6 and gelB expression in the eye become refined to the cornea and lens epithelia, iris and ciliary body, and the retinal ganglion cell layer (30,53).…”

Section: Discussionmentioning

confidence: 99%

Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B

Sivak

West‐Mays

Yee

et al. 2004

Molecular and Cellular Biology

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Pax6 is a paired box containing transcription factor that resides at the top of a genetic hierarchy controlling eye development. It continues to be expressed in tissues of the adult eye, but its role in this capacity is unclear. Pax6 is present in the adult corneal epithelium, and we showed that the amount of Pax6 is increased at the migrating front as the epithelium resurfaces the cornea after injury (J. M

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Section: Discussionmentioning

confidence: 99%

Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B

Sivak

West‐Mays

Yee

et al. 2004

Molecular and Cellular Biology

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“…For example, MMP-2 and MMP-9 were shown to be induced during hydrogen peroxide-induced cataract formation in the porcine lens [34]. UV-B irradiation was shown to induce MMP-1 expression in LECs and the same investigators showed that MMP-1 expression was induced in the lens epithelium and cortical fibers of human cortical cataracts [35].…”

Section: Matrix Metalloproteinase Expression In the Lens And Cataractsmentioning

confidence: 98%

“…In human diabetic cataracts, MMP-2 expression was also shown to be induced [36]. Human lens capsular bags were found to express both MMP-2 and MMP-9 and these MMPs were also induced following sham cataract surgery in the porcine lens [7,19,34]. Interestingly, while the majority of studies show an induction in MMPs during cataractogenesis, John et al showed that MMP inhibition, not induction, was associated with cortical cataract formation in the rat lens following oxidative stress [25].…”

Section: Matrix Metalloproteinase Expression In the Lens And Cataractsmentioning

confidence: 99%

Matrix metalloproteinases as mediators of primary and secondary cataracts

West‐Mays

Pino

2007

Expert Review of Ophthalmology

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The matrix metalloproteinases (MMPs) are a family of endopeptidases involved in numerous remodeling and fibrotic disorders. Although MMPs have been shown to play important roles in regenerative and disease processes in many parts of the eye, including the cornea, retina and trabecular meshwork, the role of MMPs in the normal and cataractous lens has only recently been studied. These investigations have shown that multiple MMPs are expressed in the lens and their expression is altered in a number of cataract phenotypes. However, anterior subcapsular cataract and posterior capsular opacification, cataracts of a fibrotic nature, show a particular involvement of MMPs. This review will highlight recent findings that suggest a causative role for MMPs in these fibrotic cataract phenotypes. Keywords cataract; EMT; fibrosis; lens; MMPIs; matrix metalloproteinase Cataract is the leading cause of blindness worldwide despite the availability of effective surgery in the developed countries [1,2]. The etiology of cataract is diverse (see Allen [3] for review) with the majority of cataracts related to aging. Extracapsular cataract extraction provides quick restoration of vision and is the most frequently performed surgical procedure in the developed world, costing over US$3.5 billion each year in the USA alone [4]. However, it is not without its problems and can lead to complications such as the development of secondary cataract (up to 40-50% incidence of patients), also known as posterior capsular opacification (PCO) [5,6]. PCO is a major medical problem with profound consequences to the patient's well-being and is a significant financial burden. PCO is considered a proliferative, fibrotic disorder that involves the aberrant deposition of matrix and wrinkling of the lens capsule [7]. Another cataract type, also of a fibrotic nature, is anterior subcapsular cataract (ASC) [6,8,9]. ASC, unlike PCO, is a primary cataract that occurs when lens epithelial cells (LECs), in situ, are stimulated to transition into myofibroblasts. These fibroblasts form subcapsular plaques directly beneath the lens capsule. Despite these differences, recent evidence has shown that in both cataract phenotypes the matrix metalloproteinases (MMPs), matrix-degrading enzymes, †Author

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“…Others have reported that lens epithelial cells grown on the lens capsule produce matrix metalloproteinases, and specifically MMP-2 and -9, when exposed to stress (Tamiya et al, 2000). To investigate whether this expression pattern would be conserved in our system, RNA was isolated from the human H36CE2 cells grown for 48 h in 0.1% (vol/vol) serum on bovine lens capsules and uncoated plastic dishes, and the expression profile for ADAMTS-1 to -20, MMP-1 to -28 and TIMP-1 to -4 were monitored by a TaqMan gene expression assays (representative result shown in Supplementary Figure 1).…”

Section: Mmps Are Expressed By Lens Cellsmentioning

confidence: 99%

FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability

Tholozan

Gribbon

et al. 2007

MBoC

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The lens is an avascular tissue, separated from the aqueous and vitreous humors by its own extracellular matrix, the lens capsule. Here we demonstrate that the lens capsule is a source of essential survival factors for lens epithelial cells. Primary and immortalized lens epithelial cells survive in low levels of serum and are resistant to staurosporine-induced apoptosis when they remain in contact with the lens capsule. Physical contact with the capsule is required for maximal resistance to stress. The lens capsule is also a source of soluble factors including fibroblast growth factor 2 (FGF-2) and perlecan, an extracellular matrix component that enhances FGF-2 activity. Matrix metalloproteinase 2 (MMP-2) inhibition as well as MMP-2 pretreatment of lens capsules greatly reduced the protective effect of the lens capsule, although this could be largely reversed by the addition of either conditioned medium or recombinant FGF-2. These data suggest that FGF-2 release from the lens capsule by MMP-2 is essential to lens epithelial cell viability and survival. INTRODUCTIONCell survival requires the continued exposure to specific survival factors. In a classic study (Ishizaki et al., 1993), lens epithelial cells were shown to survive in culture, in the absence of cell-cell contact, as long as the right growth factor cues were available. These factors could be provided exogenously either in the form of conditioned media or in serum supplement (Ishizaki et al., 1993), leading to the widely accepted general hypothesis that cells are programmed to die unless the appropriate signals are received.The recent proposal of the extracellular matrix (ECM) reservoir hypothesis suggests that the ECM itself can act as a reservoir for growth and survival factors (Bergers et al., 2000;Mott and Werb, 2004) that are released via the action of various matrix metalloproteinases (MMPs; reviewed in McCawley and Matrisian, 2001;Mott and Werb, 2004). MMPs have been shown to release fibroblast growth factor (FGF)-2 (MMP-1, -3; Whitelock et al., 1996) and fibroblast growth factor receptor (FGFR)-1 (MMP-2; Levi et al., 1996), activate transforming growth factor (TGF)-␤1/2 (Yu and Stamenkovic, 2000), and to both activate and release insulin-like growth factor (IGF)-1 (MMP-1, -2, -3, and -9;Fowlkes et al., 1994; and MMP-2, -3, and -7;Imai et al., 1997). MMPs are therefore an essential component in this proposed role for the ECM in cell survival and cell proliferation (Ishizuya-Oka et al., 2000;Wiseman et al., 2003). From such data, we can see that the ECM reservoir hypothesis requires three essential components: an ECM, growth factors sequestered by the ECM, and the presence of MMPs to release the growth factors from the ECM. This hypothesis changes our perception of the ECM as it can no longer be considered to solely provide a physical support or appropriate cues for integrin signaling (Hynes, 1992;Adams and Watt, 1993), but is also a source of cell proliferation and survival factors (Klagsbrun, 1990;Taipale and Keski-Oja, 1997;Bergers et al., 2000;...

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Induction of Matrix Metalloproteinases 2 and 9 following Stress to the Lens

Cited by 56 publications

References 34 publications

Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B

Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B

Matrix metalloproteinases as mediators of primary and secondary cataracts

FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability

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