Effect of Cyclical Mechanical Stretch and Exogenous Transforming Growth Factor-??1 on Matrix Metalloproteinase-2 Activity in Lamina Cribrosa Cells from the Human Optic Nerve Head

Kirwan, R.P.; Crean, John; Fenerty, Cecilia; Clark, Abbot F.; O’Brien, Colm

doi:10.1097/00061198-200408000-00011

Cited by 94 publications

(63 citation statements)

References 67 publications

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“…In vitro biaxial cell stretch systems have rapidly become standard models for studying the effects of mechanical forces on a variety of cell types, including trabecular meshwork cells (Bradley et al, 2001(Bradley et al, , 2003WuDunn, 2001), lamina cribrosa cells (Kirwan et al, 2004(Kirwan et al, , 2005 and scleral fibroblasts (Fujikura et al, 2002;Cui et al, 2004). These studies have attempted to model intraocular forces by introducing mechanical distortion (4 -15% increases in cellular surface area) to ocular cells for durations and frequencies ranging from <1 sec at 1 cycle/second (Kirwan et al, 2004(Kirwan et al, , 2005, 30 seconds at 2 cycles/minute (Fujikura et al, 2002), or constant stretch for 30 minutes -72 hours (Cui et al, 2004, Bradley et al, 2001.…”

Section: Discussionmentioning

confidence: 99%

“…These studies have attempted to model intraocular forces by introducing mechanical distortion (4 -15% increases in cellular surface area) to ocular cells for durations and frequencies ranging from <1 sec at 1 cycle/second (Kirwan et al, 2004(Kirwan et al, , 2005, 30 seconds at 2 cycles/minute (Fujikura et al, 2002), or constant stretch for 30 minutes -72 hours (Cui et al, 2004, Bradley et al, 2001. Because the forces exerted at the posterior ocular pole represent a combination of relatively static factors (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts

Shelton

Rada

2007

Experimental Eye Research

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In order to understand the effect of mechanical strain on scleral extracellular matrix remodeling, human scleral fibroblasts were subjected to equibiaxial stretch in vitro and the expression of proteoglycans, metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-2 (TIMP-2) were evaluated.Isolated human scleral fibroblasts were seeded onto flexible bottom culture plates, and subjected to a cyclic stretch regimen of 15% equibiaxial stretch for 45 seconds followed by 15 seconds of rest for 6 -48 hours in the presence of 35 SO 4 . Newly synthesized proteoglycans were measured in the medium by CPC precipitation of radiolabelled glycosaminoglycans. MMP-2 activity and expression levels were measured in the medium by, Western blot, gel zymography and real-time PCR. Steady state levels of TIMP-2 mRNA and membrane-type MMP, MT1-MMP (MMP-14) mRNA were measured in the cell layer using real-time PCR.The predominant gelatinolytic enzyme secreted by scleral fibroblasts was the pro-enzyme form of MMP-2 (ProMMP-2). Mechanical stretch resulted in a significant increase of ProMMP-2 after 12 and 48 hours (+76.28%, p < 0.05; +19.56%, p < 0.01, respectively). Mechanical stretch significantly increased the production of the active form of MMP-2 (ActiveMMP-2) after 48 hours (+59.72%, p < 0.05) and decreased levels of TIMP-2 mRNA (−22%, p < 0.05). The rate of scleral proteoglycan synthesis and the steady state levels of MMP-2 and MMP-14 mRNA were not significantly affected by mechanical stretch.These results suggest that mechanical strain stimulates the activation of MMP-2 by scleral fibroblasts, possibly through increased levels of ProMMP-2 and reduced levels of TIMP-2. Increased levels of ActiveMMP-2 in the sclera would be expected to contribute to scleral extracellular matrix degradation, scleral thinning and possible ocular ectasia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts

Shelton

Rada

2007

Experimental Eye Research

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“…As a result, continuous mechanically deformable pathways are going from extracellular matrix via integrins, clustered membrane-bound structures, actin- and intermediate filaments to the nuclear matrix and chromosomes (Maniotis et al, 1997a, b). Taking this into consideration, it looks but natural that several families of the developmentally important genes can be directly affected by mechanical means, namely by permanent or cyclic tension, pressure or stress relaxation (Resnik et al, 1993;Christen & Slack, 1999;Kessler et al, 2001;Chiquet et al, 2003;Brouzes &Farge,2004;Kirwan et al, 2004). Mechanical forces can also affect the transcription rate (D'Addario et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Morphomechanics: goals, basic experiments and models

Beloussov¹,

Grabovsky²

2006

Int. J. Dev. Biol.

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“…However, it is difficult to imagine how the three-dimensional structure of an embryo is regulated by genetic pathways alone. Furthermore, recent works on molecular mechanisms of embryonic development and cell differentiation have shown the context-dependency of gene expression and function (Galbraith and Sheetz, 1998;Wray and Abouheif, 1998;Chiquet, 1999;Eizinger et al, 1999;Gilbert and Sarkar, 2000;Grbic, 2000;Wu et al, 2001;Kirwan et al, 2004;Tian et al, 2004). These are the main reasons for current changes in the approach to understanding the role of epigenetic factors in development, differentiation and evolution of morphological features (Gilbert and Sarkar, 2000;Goodwin, 2000;Newman and Muller, 2000;Wilkins, 2001;Strohman, 2002).…”

Section: Introductionmentioning

confidence: 99%

Morphomechanical programming of morphogenesis in Cnidarian embryos

Kraus¹

2006

Int. J. Dev. Biol.

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The factors governing the pattern formation process in the early morphogenesis of a marine colonial hydroid, Dynamena pumila, have been studied. Two different types of morphogenesis have been distinguished. Morphogenesis of the first type goes on via changes in cell shape and cell axis orientation, while morphogenesis of the second type is based upon the active coordinated cell movements associated with cell rearrangements. It was shown that morphogenesis of both types can be considered as cascades in which any event is a consequence of the previous one. The spatial structure of each developmental stage contains information about the direction and the initial conditions of further morphogenesis. So, an "epigenetic program" of morphogenesis gradually originates in the course of development and provides the stable reproduction of spatial structures. It is reasonable to consider the activity of epigenetic factors guiding Dynamena morphogenesis (geometry/topology of an embryo, heterogeneity of an embryo spatial structure, configuration of the field of mechanical stresses of the embryo surface) as "morphomechanical programming" of morphogenesis.

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Effect of Cyclical Mechanical Stretch and Exogenous Transforming Growth Factor-??1 on Matrix Metalloproteinase-2 Activity in Lamina Cribrosa Cells from the Human Optic Nerve Head

Abstract: These results suggest that cyclical stretch and TGF-beta1 modulate MMP-2 activity in human lamina cribrosa cells. TGF-beta 1 and MMP-2 release from lamina cribrosa cells may facilitate matrix remodeling of the optic nerve head in primary open angle glaucoma.

Cited by 94 publications

References 67 publications

Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts

Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts

Morphomechanics: goals, basic experiments and models

Morphomechanical programming of morphogenesis in Cnidarian embryos

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