MMP expression in leaking filtering blebs and tears after glaucoma filtering surgery

Mathalone, Nurit; Marmor, Sylvia; Rahat, Michal A.; Lahat, Nitza; Oron, Yoram; Geyer, Orna

doi:10.1007/s00417-011-1658-0

Cited by 17 publications

(10 citation statements)

References 40 publications

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“…20,21 The MMPs also have been implicated in postoperative fibrosis after filtering surgeries and after antiglaucoma therapy. 6 It is unclear if the increased MMP activity in tears seen in our study represents actual MMP-9 upregulation in tears as a part of general inflammatory pathway activation in glaucomatous eyes or is a result of progressive leeching from the ocular surface tissues, like conjunctiva. While presence of inflammation was ruled out by clinical examination in our patients, the possibility of activation of inflammatory pathways at the ocular surface in patients naïve to medical therapy suggests the possibility of subclinical inflammation early in the disease process.…”

Section: Discussionmentioning

confidence: 86%

“…Tear film cytokines, which are regulated by tissue MMPs, are known to be differentially expressed in patients with glaucoma, which may be due to glaucoma pathogenesis or those that are altered by use of antiglaucoma drugs. 6 These cytokines have been reported to be expressed in the human tears and Tenon's capsule in the human eye, suggesting a role in ECM turnover in the ocular surface paralleling their role in ECM turnover in the TM and aqueous. 7,8 Yet, the differential MMP levels at the ocular surface in different forms and severities of glaucoma have not been explored to our knowledge.…”

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confidence: 99%

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Functional Activity of Matrix Metalloproteinases 2 and 9 in Tears of Patients With Glaucoma

Sahay

Rao

Padhy

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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[PXG]). These were compared to patients undergoing cataract surgery (controls) for this cross-sectional study. Functional activities of tear MMP-9 and MMP-2 were analyzed by gelatin zymography. Tenon's capsules (n ¼ 15) were harvested from the inferior quadrant in those undergoing cataract surgery and protein expression of MMP-9 was analyzed by immunohistochemistry (IHC). Hydrogen peroxide (H 2 O 2 ) stress-induced effects on in vitro activities of MMP-9 in human trabecular meshwork (HTM) cells were analyzed.RESULTS. The MMP-9 activity in tears was increased significantly in POAG, (n ¼ 27), PACG (n ¼ 24), and PXF (n ¼ 40) eyes compared to controls (n ¼ 35), and was increased significantly in eyes with glaucoma compared to moderate/severe glaucoma (P < 0.001). The MMP-9 expression was significantly lower in PXG (n ¼ 22) eyes. Immunohistochemistry of Tenon's capsule revealed increased expression of MMP-9 in primary glaucoma eyes. Increased MMP-9 activity was seen in in vitro by gelatin zymography and was confirmed by Western and immunofluorescent assay on HTM upon 800 and 1000 lM H 2 O 2 -induced stress for 2 to 3 hours with approximately 80% cell death. CONCLUSIONS.Increased tear MMP-9 activity in early glaucoma and pseudoexfoliation syndrome suggesting activation of extracellular matrix (ECM) degradation can be used as a tear-based predictive biomarker. Decreased expression in advanced stages suggests exhaustion of the degradation response.

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Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

Functional Activity of Matrix Metalloproteinases 2 and 9 in Tears of Patients With Glaucoma

Sahay

Rao

Padhy

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…McClusky et al [ 10 ] detected MMP-1, MMP-2, MMP-3, and TIMP-2 surrounding the conjunctival tissue of patients who underwent glaucoma drainage implant surgery. Mathalone et al [ 22 ] detected abundant MMP-9 and MMP-2 staining in the epithelial and stromal layers of the cystic leaking blebs, particularly in hypercellular and more vascularized stromal layers. They further found TIMP-1 and TIMP-2 expression in both the epithelial and stromal layers of cystic filtering blebs.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Tissue Characterization and Dynamic Expression of Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Conjunctival Filtering Bleb of Rats

Wang

Liu

Yao

2017

BioMed Research International

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Purpose Using rat conjunctival bleb model, we correlated changes morphology and histology in the bleb with changes in MMP-2 and TIMP-2 levels. Methods Filtering surgeries were performed on rats. Dynamic changes in morphology and histopathology were observed using HE staining. Expression of MMP-2 and TIMP-2 was determined by immunofluorescence microscopy and western blotting. Results Well-elevated filtering blebs formed and persisted for an average of 12 days. Histological examination showed that inflammatory was dominant in postoperative days 1–3, and proliferating manifestation became the main sign 5 days later. Western blot showed that MMP-2 was downregulated 1 day after surgery, upregulated at 3 days, and observed with a peak at 7 days; then it persisted until 28 days. The difference was statistically significant (F = 280.18, p < 0.01).TIMP-2 was upregulated 1 day after surgery and observed with a peak at 5 days; then it persisted until 28 days. The difference was statistically significant (F = 145.34, p < 0.01). Conclusions During the processes of conjunctival filtering bleb and scar formation in rats, the changes in MMP-2 and TIMP-2 levels in the filtering area, together with a corresponding proliferation of fibroblasts and the accumulation of collagen fibres, resulted in scarring of filtering blebs.

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“…On the other side attrition may lead to thinning of the conjunctiva covered by a so called attenuated epithelium [14]. In these areas the presence and action of metalloproteases may have decisive role considering survival of the bleb [15]. Additionally, they come with the risk of thinning of the bleb wall due to apoptosis and localized eradication of any wound healing response.…”

Section: Discussionmentioning

confidence: 99%

Epitheliopathy of the bleb (EoB) - identifying attrition: A new model for failure of glaucoma surgery

Setten¹

2018

New Front Ophthalmol

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Introduction: Fluorescein staining of the ocular surface is used to detect anomalies and damage of the ocular surface. The intensity of staining and its pattern does reflect underlying pathology and severity. We have recently reported on the presence of sandbank epitheliopathy and its specific staining of the conjunctival surface. As glaucoma surgery is known to alter ocular tissues structures we investigated if it might cause a characteristic footpint at the ocular surface.

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MMP expression in leaking filtering blebs and tears after glaucoma filtering surgery

Abstract: Increased MMPs and TIMPs expression is associated with the formation of filtering blebs, suggesting involvement of MMPs in bleb remodeling. MMP-2 and ProMMP-2 levels in tear fluid may be markers for bleb configuration.

Cited by 17 publications

References 40 publications

Functional Activity of Matrix Metalloproteinases 2 and 9 in Tears of Patients With Glaucoma

Functional Activity of Matrix Metalloproteinases 2 and 9 in Tears of Patients With Glaucoma

Correlation between Tissue Characterization and Dynamic Expression of Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Conjunctival Filtering Bleb of Rats

Epitheliopathy of the bleb (EoB) - identifying attrition: A new model for failure of glaucoma surgery

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