Elevated Expression and Activation of Matrix Metalloproteinase 8 in Tear Fluid in Atopic Blepharoconjunctivitis

Määttä, Marko; Kari, Osmo; Tervahartiala, Taina; Wahlgren, Jaana; Peltonen, Sirje; Kari, Marjatta; Rytilä, Paula; Saari, Mohd Yusof; Sorsa, Timo

doi:10.1097/ico.0b013e31815c18d6

Cited by 21 publications

(7 citation statements)

References 33 publications

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“…Our study shows that the proteolytic enzyme activity is increased in NAEC: the mean MMP-8 concentration of in NAEC tears is significantly higher (3-to 4-fold higher) than for the healthy controls. We have recently demonstrated that in atopic eosinophilic blepharoconjunctivitis (ABC) patients, the MMP-8 concentration in tears was also significantly increased [24]. However, among ABC patients, the mean MMP-8 concentration was two to three times higher than among NEAC patients, which seems to separates them from the NAEC group, and further suggests that NAEC is a independent entity among chronic conjunctivitis.…”

Section: Discussionmentioning

confidence: 91%

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Kari

Määttä

Tervahartiala

et al. 2009

Graefes Arch Clin Exp Ophthalmol

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Section: Discussionmentioning

confidence: 91%

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Kari

Määttä

Tervahartiala

et al. 2009

Graefes Arch Clin Exp Ophthalmol

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“…Studies on the cornea in vitro and in vivo have underscored the role of MMPs in normal and pathological epithelial wound healing, stromal remodeling and corneal ulceration 9,10 . Furthermore, studies of human tears showed elevated levels and activities of MMPs in inflammatory ocular surface diseases such as dry eye 11 , infective keratitis 12 , active peripheral ulcerative keratitis 13 , atopic blepharoconjunctivitis 14 , ocular rosacea 15 , vernal conjunctivitis 16 and non-allergic eosinophilic conjunctivitis 17 . Inflammatory cells, particularly neutrophils, are major sources of neutrophil collagenase (MMP-8) and gelatinase B (MMP-9), both of which have been associated with the extent of cellular inflammation 12,14,18,19 .…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Collagenase, Gelatinase, and Myeloperoxidase in Tears of Patients with Stevens-Johnson Syndrome and Ocular Cicatricial Pemphigoid

et al. 2014

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Objective To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Design Prospective non-interventional cohort study. Participants Four SJS patients (7 eyes), 19 OCP patients (37 eyes) and 20 post-phacoemulsification healthy controls (40 eyes). Methods Tear washes were collected from all patients and were analyzed for levels of MMP-2, -3, -7, -8, -9, -12, MPO and TIMP-1 using multi-analyte bead-based enzyme-linked immunosorbent assays (ELISA). Total MMP activity was determined using a fluorimetric assay. Correlation studies were performed between the various analytes within study groups. Main Outcome Measures Levels of MMP-2, -3, -7, -8, -9, -12, MPO and TIMP-1 (in ng/µg protein), total MMP activity (in relative fluorescent units/min/µg protein) in tears, MMP-8/TIMP-1, MMP-9/TIMP-1 ratios and the correlations between MMP-8 and MMP-9 and each MMP and MPO. Results MMP-8, MMP-9 and MPO levels were significantly elevated in SJS and OCP tears (SJS > OCP) when compared to controls. MMP activity was highest in SJS while OCP and controls showed lower and similar activities. TIMP-1 levels were decreased in SJS and OCP when compared to controls with OCP levels reaching significance. MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS > OCP) when compared to controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels and MMP-8 correlated with MPO but did not reach significance in SJS. There was no relationship between MMP-7 and MPO. Conclusions Since MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes including MMP-9 in SJS and OCP tears. Elevated MMP/TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to develop corneal melting and chronic complications associated with persistent inflammation. MPO in tears may be a sensitive and specific marker for the quantification of ocular inflammation.

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“…Specifically, MMP-2 and MMP-9 are gelatinases that degrade type IV collagen, the major structural component of the ECM [4]. These proteases were found to take part in many ocular disorders like retinopathy [5], cataract [6], uveitis [7], or generally atopic ocular diseases [8]. In turn, local micromolar NO concentrations may exert similar effects that are connected with inflammation and local tissue destruction.…”

Section: Introductionmentioning

confidence: 99%

The impact of oleanolic and ursolic acid on corneal epithelial cells in vitro

et al. 2017

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introduCtion. Oleanolic (OA) and ursolic (UA) acids belong to the triterpene group widely present in plants. These compounds are recognised to have anti-inflammatory properties and thus are considered to be used in therapies as well as in cosmetic, natural health, or diet products. aiM. The scientific hypothesis of our study was to show that OA and UA influence corneal epithelial cells cultured in vitro. Methods. Toxicity tests, based on MTT and Neutral Red (NR) uptake, measurement of nitric oxide (NOx) level, as well as analysis of metalloproteinases (MMP-2 and MMP-9) amount and activity were performed. resuLts. UA expressed significantly higher toxicity on cells than OA. At the lowest concentration applied (5 µM), UA limited cellular metabolism and viability on average by 22% as compared to untreated control, while 25 µM resulted in values lower than 10%. On the other hand, OA at the highest (100 µM) concentration limited cellular metabolism and viability by about 20%. NOx level significantly increased when OA and UA were applied at concentrations of 25 and 100 µM, respectively. OA and UA had a stronger impact on the level of MMP-2 than MMP-9. OA and UA reduced MMP-2 and MMP-9 in the whole range of concentrations. Tested triterpenoids had no significant impact on MMP activity. ConCLusions. OA and UA have a different impact on human corneal epithelial cells. UA is toxic for corneal epithelial cells, while OA exhibits milder activity, which may be useful for further analysis in ocular pharmacology.

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Elevated Expression and Activation of Matrix Metalloproteinase 8 in Tear Fluid in Atopic Blepharoconjunctivitis

Abstract: : A higher mean concentration and activation of MMP-8 is present in tear fluid in ABC. This finding probably reflects persistent inflammatory and collagenolytic activity associated with the disease.

Cited by 21 publications

References 33 publications

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Neutrophil Collagenase, Gelatinase, and Myeloperoxidase in Tears of Patients with Stevens-Johnson Syndrome and Ocular Cicatricial Pemphigoid

The impact of oleanolic and ursolic acid on corneal epithelial cells in vitro

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