Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular matrix turnover in the trabecular meshwork may play a role in regulating aqueous humor outflow. Laser trabeculoplasty is a common treatment for open-angle glaucoma. The mechanism of this treatment is not understood. We investigated changes in the levels and expression of the matrix metalloproteinases and their tissue inhibitors (TIMPs) in this tissue using cultured human anterior segment explants and standard clinical-parameter laser treatment. Medium gelatinase A activity levels are relatively high for sham-treated controls and are not changed dramatically following laser treatment. Medium gelatinase B and stromelysin activity levels are low in sham-treated explants and increase significantly by 24 h after treatment. TIMP1 levels, as assessed by immunoblots of Western transfers, are initially low. However, by 24 h TIMP1 levels have increased significantly. Using semi-quantitative reverse transcription and the polymerase chain reaction, mRNA levels of stromelysin, gelatinase B and TIMP1 are shown to increase after laser treatment, while gelatinase A and TIMP2 remain relatively constant. The increases in trabecular stromelysin and gelatinase B in response to laser trabeculoplasty may have important implications for the mechanism of action of this treatment for open-angle glaucoma.
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PMID:Early changes in matrix metalloproteinases and inhibitors after in vitro laser treatment to the trabecular meshwork. 758 99

Steroid-induced glaucoma is believed to result from increased aqueous outflow resistance and evidence suggests that this is the result of an excess accumulation of extracellular matrix components. This accumulation could result from an imbalance in the natural turnover of these components. We have investigated the effect of corticosteroid treatment of trabecular meshwork (TM) organ and cell cultures on the extracellular activities of the matrix metalloproteinases and plasminogen activators. We find that corticosteroid treatment results in decreased extracellular activity of stromelysin and tissue plasminogen activator in trabecular meshwork cell culture, and decreased 92 kDa collagenase IV, stromelysin, and tissue plasminogen activator in trabecular meshwork organ culture. These data suggest that decreased levels of proteolytic activities could account, in part, for the accumulation of some extracellular matrix components and be a contributing mechanism in steroid-induced glaucoma.
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PMID:Corticosteroid treatment and trabecular meshwork proteases in cell and organ culture supernatants. 828 32

Loss of retinal ganglion cells is the final end point in blinding diseases of the optic nerve such as glaucoma. To enable the use of mouse genetics to investigate mechanisms underlying ganglion cell loss, we adapted an experimental model of optic nerve ligation to the mouse and further characterized post-surgical outcome. We made the novel finding that apoptosis of retinal ganglion cells correlates with specific degradation of laminin from the underlying inner limiting membrane and an increase in gelatinolytic metalloproteinase activity. These changes co-localize with a specific increase in levels of the matrix metalloproteinase, gelatinase B (GelB; MMP-9). Using a transgenic mouse line harboring a reporter gene driven by the GelB promoter, we further show that increased GelB is controlled by activation of the GelB promoter. These findings led us to hypothesize that GelB activity plays a role in ganglion cell death and degradation of laminin. Applying the genetic approach, we demonstrate that GelB-deficient mice are protected against these pathological changes. This is the first report demonstrating a causal connection between GelB activity and pathological changes to the inner retina after optic nerve ligation.
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PMID:Deficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation. 1235 72

The goal of glaucoma filtering surgery is to create a low resistance pathway for aqueous outflow. The result is a blister or 'bleb' on the conjunctiva, from which fluid drains into the vasculature. Filtering surgery results may be compromised if blebs develop leaks, a problem that surfaces more frequently when antimetabolites are used to control the wound healing response. We investigated the role of tissue remodelling enzymes of the Matrix metalloproteinase (MMP) family in the development of bleb leaks. Our design was a case series. We enrolled glaucoma patients with leaking blebs, glaucoma patients with overhanging blebs and normal eyes. Leaking bleb tissues (n=11) and bleb leak fluid were collected from patients undergoing bleb revision surgery. Overhanging bleb tissues (from non-leaking blebs, n=3), normal conjunctiva (n=8), and aqueous humour (n=4) were collected for comparison. Samples were analysed for MMP content and proteinase activity by the methods of zymography, western blotting, immunohistochemistry, and in situ zymography. Our main outcome measures were presence and activity of MMP in sample. Zymography revealed the presence of a high molecular weight caseinase and a 92-kDa gelatinase of a size appropriate for the proenzyme form of gelatinase B (gelB; MMP-9), in extracts from leaking bleb tissue, but not in bleb leak fluid or aqueous humour samples. In contrast, a 65-kDa gelatinase of a size appropriate for gelatinase A (MMP-2) proenzyme was observed in all samples. All proteinases disappeared when 10mm EDTA was added to the development buffer, consistent with their identity as MMPs. Western blotting and immunohistochemical analyses confirmed the identity of the 92kDa proteinase as gelB, and further revealed its absence from extracts of overhanging bleb tissue and normal conjunctiva. In situ zymography demonstrated strong gelatinolytic activity in leaking bleb tissue, but not overhanging bleb tissue or normal conjunctiva. MMP-g may be involved in the mechanism of formation of bleb leaks. Precise description of the cascade of events leading to bleb leakage may allow the design of therapeutic interventions to prevent, stabilize or reverse bleb leakage.
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PMID:Matrix metalloproteinase gelatinase B (MMP-9) is associated with leaking glaucoma filtering blebs. 1618 54

Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K(i)=13.2nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.
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PMID:Characterization of a novel non-steroidal glucocorticoid receptor antagonist. 2003 23

Retinal ganglion cells apoptosis is linked to matrix metalloproteinase 9 (MMP-9) controlled changes of extracellular matrix. Abnormal expression of MMP-9 is associated with glaucomatous alterations. Thus, the knowledge of MMP-9 regulation is important for the understanding the pathogenesis of glaucoma. Here, we investigated the role of 3'-untranslated regions (3'-UTR) and microRNAs in MMP-9 regulation. We used in vitro mutagenesis and Luc reporter system to identify regulatory elements in the 3'-UTR of MMP-9. microRNAs were analyzed by qRT-PCR, and their role was investigated with inhibitors and mimics. We identified targets for miRNAs in 3'-UTR of MMP-9 involved in the regulation of MMP-9 expression. We then isolated miRNAs from the optic nerve A7 astrocytes and 293 T cells and confirmed the role of mi340 in the regulation using specific inhibitors and mimics. The results obtained show a new miRNA-mediated mechanism of MMP-9 expression regulation.
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PMID:Matrix metalloproteinase 9 expression: new regulatory elements. 2181 6