Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the role of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1 and TIMP-2) in intraocular diseases, levels of TIMP-1 and TIMP-2 were measured by enzyme immunoassay in 47 patients with various ocular diseases: in subretinal fluid of 7 patients with rhegmatogenous retinal detachment and in vitreous of 12 patients with proliferative diabetic retinopathy, 4 with proliferative vitreoretinopathy, 2 with vitreous hemorrhage due to branch retinal vein occlusion, 12 with idiopathic macular hole, 3 with retinal detachment due to high-myopic macular hole, 4 with macular epiretinal membrane, and 3 with choroidal neovascular membrane due to age-related macular degeneration. TIMP-1 levels were significantly higher in subretinal fluid than in vitreous fluid with any diseases (P < 0.0001, Mann-Whitney U test). TIMP-1 levels in vitreous fluid of the eyes with proliferative diabetic retinopathy and proliferative vitreoretinopathy were higher than those in vitreous with other diseases (P < 0.0001). In contrast, TIMP-2 levels were not elevated in the subretinal fluid and vitreous. TIMP-1, but not TIMP-2, was secreted into the subretinal space in rhegmatogenous retinal detachment, and also into the vitreous in eyes with proliferative disease, suggesting that TIMP-1 would play a specific role in the process of these diseases.
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PMID:TIMP-1 and TIMP-2 levels in vitreous and subretinal fluid. 982 66

Matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs) play an important role in matrix remodelling and their involvement in the formation of scar-like tissue in proliferative vitreoretinopathy (PVR) is unknown. In this study we investigated epiretinal and subretinal membranes of PVR for the presence of selected MMPs and TIMPs whose substrates are extracellular matrix components of these membranes. We examined 23 epiretinal membranes and 15 subretinal membranes of PVR for deposition of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase A (MMP-2), gelatinase B (MMP-9) and two tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) by immunohistochemical methods. Normal cadaveric retinas served as controls. We observed that a large proportion of epiretinal and subretinal membranes stained for MMP-1 and MMP-2, whilst MMP-3, MMP-9, TIMP-1 and TIMP-2 were only observed in a small proportion of specimens. Normal cadaveric retinas stained for MMP-1 but not for MMP-2, MMP-3, MMP-9 or TIMP-1. TIMP-2 positive cells were observed within the inner and outer nuclear cell layers of normal retina. Presence of MMP-2, MMP-3 and TIMP-1 in epiretinal and subretinal membranes of PVR but not in normal retina indicates that these molecules may play an important role during the healing process that follows rhegmatogenous retinal detachment. An understanding of the mechanisms that control production and activity of these enzymes and their inhibitors may aid in the design of new therapeutic approaches to treat and prevent PVR.
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PMID:Predominance of MMP-1 and MMP-2 in epiretinal and subretinal membranes of proliferative vitreoretinopathy. 998 46

The most common cause of failure of retinal reattachment surgery is formation of fibrocellular contractile membranes on both surfaces of the neuroretina. This intraocular fibrosis, known as proliferative vitreoretinopathy, results in a blinding tractional retinal detachment because of the contractile nature of the membrane. Contractility is a cell-mediated event that is thought to be dependent on locomotion and adhesion to the extracellular matrix. Interactions between cells and the extracellular matrix can be influenced by matrix metalloproteinases (MMPs) and we investigated the role of MMPs in two in vitro models (two- and three-dimensional) of human retinal pigment epithelial (RPE) cell-mediated contraction. MMP activity was detected using enzyme-linked immunosorbent assays and zymography techniques that revealed MMP-1, -2, -3, and -9 positivity during the collagen matrix contraction assays. RPE-populated collagen matrix contraction (three-dimensional) was inhibited using a cocktail of anti-MMP antibodies and with Galardin (a broad-spectrum MMP inhibitor). Galardin inhibition was dose-dependent, reversible, and dependent on cell number. MMP inhibitors had no effect on contraction when RPEs were seeded on two-dimensional collagen matrices or on cellular adhesion to collagen type I. Our results suggest that MMP activity may be required for three-dimensional but not two-dimensional RPE-collagen matrix contraction.
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PMID:Matrix metalloproteinases: a role in the contraction of vitreo-retinal scar tissue. 1158 81

Cell detachment is a procedure routinely performed in cell culture and a necessary step in many biochemical assays including the determination of oxygen consumption rates (OCR) in vitro. In vivo, cell detachment has been shown to exert profound metabolic influences notably in cancer but also in other pathologies, such as retinal detachment for example. In the present study, we developed and validated a new technique combining electron paramagnetic resonance (EPR) oximetry and the use of cytodex 1 and collagen-coated cytodex 3 dextran microbeads, which allowed the unprecedented comparison of the OCR of adherent and detached cells with high sensitivity. Hence, we demonstrated that both B16F10 melanoma cells and human umbilical vein endothelial cells (HUVEC) experience strong OCR decrease upon trypsin or collagenase treatments. The reduction of cell oxygen consumption was more pronounced with a trypsin compared to a collagenase treatment. Cells remaining in suspension also encounter a marked intracellular ATP depletion and an increase in the lactate production/glucose uptake ratio. These findings highlight the important influence exerted by cell adhesion/detachment on cell respiration, which can be probed with the unprecedented experimental assay that was developed and validated in this study.
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PMID:Influence of cell detachment on the respiration rate of tumor and endothelial cells. 2338 41