Enzymatic Breakdown of Type II Collagen in the Human Vitreous (original) (raw)
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Trypsin-mediated enzymatic degradation of type II collagen in the human vitreous
Molecular vision, 2013
Aging of the vitreous body can result in sight-threatening pathology. One aspect of vitreous aging is liquefaction, which results from the vanishing of collagen fibrils. We investigated the possibility that trypsins are involved in vitreous type II collagen degradation. Immunohistochemistry and western blotting were used for detecting and locating trypsin isoforms in the vitreous and retina of human donor eyes. The capability of the retina to produce these trypsins was analyzed with polymerase chain reaction. Whether the different trypsins degraded type II collagen was tested in vitro. The sizes of the in vitro induced type II collagen degradation products were compared to those present in the vitreous of human eyes of different ages. Trypsin-1 and trypsin-2 were detected in the vitreous. In the retina, messenger ribonucleic acid (mRNA) coding for trypsin-2, -3, and -4 was present. Using immunohistochemistry, trypsin-2 was detected in microglial cells located in the vitreous and the...
Experimental Eye Research, 2005
The purpose of this study was to evaluate the vitreoretinal border in the (pre-)equatorial area in nonpathologic human donor eyes, because the majority of retinal defects induced by posterior vitreous detachment (PVD) are located there. Nine eyes (24-80 years) were fixed and embedded in Technovit 8100. After evaluation by light microscope, areas of interest were selected for immunotransmission electron microscope. Anti-type II collagen antibody was used to stain vitreous fibrils and lamellae; anti-type IV collagen antibody was used to identify the internal limiting lamina (ILL); anti-vimentin and anti-CD-68 antibodies stained retinal Müller cells and macrophages, respectively. Observations included fusing of lamellae with the ILL, an intravitreal course of the ILL, and clear focal interruptions in the ILL. In addition, an obvious finding was the presence of intraretinal packages of type II collagen. Interestingly these collagen packages were closely related to Müller cells and, in several eyes, also to macrophages, cell debris and interruptions in the ILL. In our opinion, the collagen packages can reflect the net result of a process of interactive remodelling, in which both breakdown and synthesis of vitreous and ILL collagens take place. Connections between vitreous and intraretinal collagen networks can make the (pre-)equatorial area more vulnerable to tearing and retinal detachment in the case of liquefaction and PVD. q
Matrix Biology, 1999
. Recent data suggest that gelatinase A matrix metalloproteinase-2, MMP-2 plays an important role in the degradation of collagen of soft connective tissues. In an attempt to investigate its participation in more detail we assessed the digestion of collagen in cultured rabbit periosteal explants and compared this with the level of active MMP-2 and collagenases. The data demonstrated that both collagen degradation and MMP activity increased with time. Conditioned medium obtained from Ž explants cultured for 72 h showed that the level of active MMP-2 correlated with collagen degradation r s 0.80, d.f.s 23, . Ž . P -0.0001 . Such a relationship was not found with collagenase activity r sy0.08, d.f.s 21, NS . The possible involvement of Ž MMP-2 in collagen degradation was investigated further by incubating explants with selective gelatinase inhibitors CT1166, . Ž . CT1399 and CT1746 . In the presence of these compounds breakdown of collagen was almost completely abolished f 80% . Finally we assessed whether periosteal fibroblasts had the capacity to degrade collagen type I that conferred resistance to collagenase activity. Breakdown of this collagen did not differ from degradation of normal collagen. Taken together, our data provide support for the view that MMP-2 plays a crucial role in collagen degradation of soft connective tissue. ᮊ : S 0 9 4 5 -0 5 3 X 9 9 0 0 0 3 2 -3 ( ) E.H. Kerk¨liet et al. r Matrix Biology 18 1999 373᎐380 374
Influence on collagen metabolism of vitreous from eyes with proliferative vitreoretinopathy
Ophthalmology, 1995
Purpose: Proliferative vitreoretinopathy (PVR) is characterized by cell proliferation and membrane formation on the vitreoretinal cavity of the eye. The membranes are composed of extracellular matrix, mainly collagen type I. To explore the possible mechanisms involved in PVR membrane formation, the authors analyzed the role of vitreous humor on collagen turnover.
Collagenolytic/Gelatinolytic Enzymes in Corneal Wound Healing
Acta Ophthalmologica, 2009
We have documented changes in expression of collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in healing or ulcerating corneal wounds of rat or rabbit. Correlation of our findings with specific changes in the extracellular matrix of the repair tissue suggests two different roles for the enzymes, MMP-2 and MMP-9. MMP-2 is expressed in undamaged corneal stroma where it may degrade the occasional collagen molecule that becomes damaged. After corneal wounding, expression of this enzyme is increased and much of it appears in the active form. These changes persist for at least seven months, suggesting that MMP-2 is involved in the prolonged process of collagen remodelling in the stromal repair tissue. MMP-9 is expressed in the epithelial layer of repair tissue with a timing suggesting it might participate in controlling resynthesis of the basement membrane. MMP-9 also appears to be involved in degradation of the epithelial basement membrane that precedes corneal ulceration.
Effects of Collagenase Type II on Vitreous Humor—An In Situ Rheological Study
Journal of Biomechanical Engineering, 2019
The purpose of this study is to quantify the impact of enzyme activity on the vitreous humor structure over time to understand the mechanical characteristics of the vitreous humor gel. Changes in the mechanical behavior of the vitreous occur due to many reasons including aging, which may lead to many vitreoretinal diseases. The degeneration process of the vitreous has been studied; however, in situ experimental procedures to validate the existing hypotheses are limited. We examined thirty-eight porcine eyes using in situ rheological creep tests to measure the mechanical properties of the vitreous humor of the eyes prior to, 1 h and 24 h after the intravitreal injection. Eyes in one group were injected with collagenase type II solution and eyes in the control group were injected with phosphate buffered saline solution (PBS) with calcium and magnesium chloride. Prior to the injection, viscosity and creep compliance intercept values between both groups were not statistically different....
MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology
Progress in Retinal and Eye Research, 2002
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that function to maintain and remodel tissue architecture. Their substrates represent an astounding variety of extracellular matrix components, secreted cytokines and cell surface molecules, and they have been implicated in a wide range of processes and diseases. To date MMPs have been found in virtually every tissue of the eye under conditions of health and disease. Although their functions in vivo remain poorly understood, it is clear they impact on essentially every aspect of eye physiology. This chapter reviews the expanding literature on MMPs in the eye and attempts to place it in the context of basic MMP biology. A general overview of MMP functions is presented first, and then the discussion moves to examples of possible MMP roles in two eye structures. For the cornea, we present recent work on the roles of MMPs during various aspects of wound healing. For the retina, we describe the activities of MMPs in specific disease states from which common principles may emerge. r
Roles of matrix metalloproteinases in the cornea: A special focus on macular corneal dystrophy
Medicine in Drug Discovery, 2021
Matrix metalloproteinases (MMPs) are endopeptidases that are responsible for the degradation of several components of the extracellular matrix (ECM) and some non-ECM proteins. MMPs are subdivided into 6 groups according to their structure and substrate specificity: collagenases, gelatinases, membrane-type MMPs, stromelysins, and matrilizines. Collagenases are important proteolytic tools during ECM remodeling, tissue regeneration, and organ development. MMPs, especially collagenases, have important roles in ocular processes such as retinal neurogenesis and corneal wound healing. MMP studies on eye research are limited, but there is growing evidence that MMP physiology is key for the ocular system, especially for the cornea. The cornea is predominantly composed of collagen fibrils, which form uniform lamellar lattices. Collagenase-driven ECM remodeling is essential for the cornea. Macular corneal dystrophy (MCD) is a rare inherited disease and characterized by progressive, insoluble accumulation of irregular substances in the corneal ECM. MCD can cause visual acuity loss up to blindness, and there is currently no treatment available. It has been recently reported that certain collagenases are downregulated in MCD disease progression. Here, we review the roles of MMPs in eye diseases and propose possible treatment strategies for MCD. Contents