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Timo Tervo - One of the best experts on this subject based on the ideXlab platform.
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Elevation of Tear Fluid plasmin in corneal disease.
Acta Ophthalmologica, 2009Co-Authors: Timo Tervo, A. Vahen, G.‐b. Setten, Ilkka Immonen, E M Salonen, Jaakko-juhani Himberg, Ahti TarkkanenAbstract:. Plasmin concentration was determined in Tear Fluid from 76 eyes showing corneal epithelial disorders, such as corneal ulcers and erosions due to trauma or contact lens wear. Nearly 70% of the eyes with corneal disease had plasmin in their Tear Fluid, whereas plasmin was present in only 20% of the eyes in a control group of 50 eyes. Re-examination of the plasmin positive control eyes revealed conjunctival bacterial growth or mild subclinical viral infection in most cases. We conclude that plasmin is released into the Tear Fluid in the presence of corneal or conjunctival lesions or infections, suggesting a pathogenic role of plasmin in these disorders. The significance of the occurrence of plasmin in Tear Fluid during corneal wound healing is discussed.
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Tear Fluid plasmin activity of dry eye patients with Sjögren's syndrome.
Acta ophthalmologica Scandinavica, 2009Co-Authors: Tuula Virtanen, Matti Härkönen, Yrjö T. Konttinen, Niina Honkanen, Timo TervoAbstract:Thirty-two eyes of 16 patients with verified Sjogren's syndrome were examined for clinical signs of dry eye. Tear Fluid samples were collected for plasmin assay. Ophthalmologic examinations included estimation of conjunctival or corneal discharge, filament formation and presence of conjunctival or corneal epithelial defects, assessment of Tear meniscus height and measurement of Tear Fluid break-up time, Schirmer test, and fluorescein and Rose-Bengal staining graded by the van Bijsterveld score. Tear Fluid plasmin activity (IU/l) was determined by a fluorometric assay and Tear Fluid flow (microl/min) was measured for calculation of Tear Fluid plasmin activity release (microIU/min). All patients had relatively dry eyes; the mean Schirmer test value was 5.7 +/- 0.5 mm/5 min. The mean Tear Fluid break-up time was also low, 7.7 +/- 0.5 s. The mean Bijsterveld score value was 2.5 +/- 0.5. Because collection of Tear Fluid by microcapillaries for the plasmin assay was difficult due to the low Tear Fluid flow rate, it was necessary to drop 20 microl of balanced salt solution topically on the cornea to aspirate a Tear Fluid sample. Despite this, the mean Tear Fluid plasmin activity was higher than in control individuals (7.75 +/- 1.51 IU/l vs. 0.73, range 0.64-0.80 IU/l). On the basis of these findings we conclude that elevated Tear Fluid proteolytic activity may play a role in the pathology of dry eye/ocular surface disease.
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Plasmin in Tear Fluid of patients with corneal ulcers: basis for new therapy.
Acta ophthalmologica, 2009Co-Authors: E M Salonen, Ahti Tarkkanen, Timo Tervo, Esa Törmä, Antti VaheriAbstract:. In a patient with chronic corneal ulcer, resistant to conventional therapy, analysis of Tear Fluid revealed a high plasmin activity which could be inhibited by aprotinin, an inhibitor of serine proteinases. Therapy with topical aprotinin resulted in rapid epithelialization. After this initial patient, within a period of four months Tear Fluid specimens of altogether 48 patients with corneal lesions were analyzed, and 32 were found to be positive for proteolytic activity. Of these 18 were treated with topical aprotinin which rapidly promoted corneal epithelial healing. Six of these patients had been treated with conventional therapy for 3–10 weeks but proved to be completely therapy-resistant. Our observations on three successfully treated patients with chemical burns of the cornea indicated appearance of plasmin in Tear Fluid after a few days correlating with cessation of epithelialization. In all patients, in which Tear Fluid plasmin activity was followed, the activity disappeared during aprotinin therapy correlating with corneal re-epithelialization. In some patients with low proteolytic activity aprotinin was combined with fibronectin with a beneficial therapeutic effect. No proteolytic activity was found in the Tear Fluid of control individuals. These preliminary data indicate that in patients with treatment-resistant corneal lesions inhibition of proteolytic activity can assist in epithelial healing. Such an inhibition is likely to be a prerequisite for the proteinase-sensitive cell adhesion proteins such as fibronectin to promote epithelialization.
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Phospholipid Transfer Protein Is Present in Human Tear Fluid
Biochemistry, 2005Co-Authors: Matti Jauhiainen, Timo Tervo, Niko L. Setälä, Christian Ehnholm, Jari Metso, Ove Eriksson, Juha M. HolopainenAbstract:The human Tear Fluid film consists of a superficial lipid layer, an aqueous middle layer, and a hydrated mucin layer located next to the corneal epithelium. The superficial lipid layer protects the eye from drying and is composed of polar and neutral lipids provided by the meibomian glands. Excess accumulation of lipids in the Tear film may lead to drying of the corneal epithelium. In the circulation, phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) mediate lipid transfers. To gain insight into the formation of Tear film, we investigated whether PLTP and CETP are present in human Tear Fluid. Tear Fluid samples were collected with microcapillaries. The presence of PLTP and CETP was studied in Tear Fluid by Western blotting, and the PLTP concentration was determined by ELISA. The activities of the enzymes were determined by specific lipid transfer assays. Size-exclusion and heparin-affinity chromatography assessed the molecular form of PLTP. PLTP is present in Tear Fluid, whereas CETP is not. Quantitative assessment of PLTP by ELISA indicated that the PLTP concentration in Tear Fluid, 10.9 +/- 2.4 microg/mL, is about 2-fold higher than that in human plasma. PLTP-facilitated phospholipid transfer activity in Tears, 15.1 +/- 1.8 micromol mL(-)(1) h(-)(1), was also significantly higher than that measured in plasma. Inactivation of PLTP by heat treatment (+58 degrees C, 60 min) or immunoinhibition abolished the phospholipid transfer activity in Tear Fluid. Size-exclusion chromatography of Tear Fluid indicated that PLTP eluted in a position corresponding to a size of 160-170 kDa. Tear Fluid PLTP was quantitatively bound to Heparin-Sepharose and could be eluted as a single peak by 0.5 M NaCl. These data indicate that human Tear Fluid contains catalytically active PLTP protein, which resembles the active form of PLTP present in plasma. The results suggest that PLTP may play a role in the formation of the Tear film by supporting phospholipid transfer.
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Wound Healing Modulators in Tear Fluid
Advances in Corneal Research, 1997Co-Authors: Timo Tervo, Minna VesaluomaAbstract:Unexpected variations in corneal wound healing affect the predictability of photorefractive keratectomy (PRK). Several modulators coming from Tears, inflammatory cells, extracellular matrix, nerve cells, corneal epithelial cells, or stromal fibroblasts can regulate the complex wound healing process. This report evaluates the presence and release of these modulators in Tear Fluid following PRK. The release of plasmin, cellular fibronectin, tenascin and calcitonin gene-related peptide (CGRP) into Tears following excimer laser keratectomy has been shown to be increased during the first postoperative days. Lately studies have focused on growth factors/cytokines. The release of hepatocyte growth factor (HGF), transforming growth factor-βl (TGF-βl), vasoendothelial growth factor (VEGF), and tumor necrosis factor-α (TNF-α) in Tear Fluid is also significantly increased during the first two days after excimer laser-induced corneal wound. These healing modulators are likely to regulate epithelial differentiation, proliferation, and migration; cell-to-cell and cell-to-matrix interactions; stromal extracellular matrix production; and transition of keratocytes into contractile myofibroblast-like cells. They are possibly also involved in the formation of postoperative stromal scar.
Ahti Tarkkanen - One of the best experts on this subject based on the ideXlab platform.
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Elevation of Tear Fluid plasmin in corneal disease.
Acta Ophthalmologica, 2009Co-Authors: Timo Tervo, A. Vahen, G.‐b. Setten, Ilkka Immonen, E M Salonen, Jaakko-juhani Himberg, Ahti TarkkanenAbstract:. Plasmin concentration was determined in Tear Fluid from 76 eyes showing corneal epithelial disorders, such as corneal ulcers and erosions due to trauma or contact lens wear. Nearly 70% of the eyes with corneal disease had plasmin in their Tear Fluid, whereas plasmin was present in only 20% of the eyes in a control group of 50 eyes. Re-examination of the plasmin positive control eyes revealed conjunctival bacterial growth or mild subclinical viral infection in most cases. We conclude that plasmin is released into the Tear Fluid in the presence of corneal or conjunctival lesions or infections, suggesting a pathogenic role of plasmin in these disorders. The significance of the occurrence of plasmin in Tear Fluid during corneal wound healing is discussed.
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Plasmin in Tear Fluid of patients with corneal ulcers: basis for new therapy.
Acta ophthalmologica, 2009Co-Authors: E M Salonen, Ahti Tarkkanen, Timo Tervo, Esa Törmä, Antti VaheriAbstract:. In a patient with chronic corneal ulcer, resistant to conventional therapy, analysis of Tear Fluid revealed a high plasmin activity which could be inhibited by aprotinin, an inhibitor of serine proteinases. Therapy with topical aprotinin resulted in rapid epithelialization. After this initial patient, within a period of four months Tear Fluid specimens of altogether 48 patients with corneal lesions were analyzed, and 32 were found to be positive for proteolytic activity. Of these 18 were treated with topical aprotinin which rapidly promoted corneal epithelial healing. Six of these patients had been treated with conventional therapy for 3–10 weeks but proved to be completely therapy-resistant. Our observations on three successfully treated patients with chemical burns of the cornea indicated appearance of plasmin in Tear Fluid after a few days correlating with cessation of epithelialization. In all patients, in which Tear Fluid plasmin activity was followed, the activity disappeared during aprotinin therapy correlating with corneal re-epithelialization. In some patients with low proteolytic activity aprotinin was combined with fibronectin with a beneficial therapeutic effect. No proteolytic activity was found in the Tear Fluid of control individuals. These preliminary data indicate that in patients with treatment-resistant corneal lesions inhibition of proteolytic activity can assist in epithelial healing. Such an inhibition is likely to be a prerequisite for the proteinase-sensitive cell adhesion proteins such as fibronectin to promote epithelialization.
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Tear Fluid Plasmin Activity After Excimer Laser Photorefractive Keratectomy
Investigative ophthalmology & visual science, 1994Co-Authors: Timo Tervo, Tuula Virtanen, N. Honkanen, Matti Härkönen, Ahti TarkkanenAbstract:PURPOSE Elevated Tear Fluid plasmin activity may correlate with delayed healing of corneal wounds. The present study was performed to establish the Tear Fluid plasmin activity after photorefractive keratoablation (PRK). METHODS Tear Fluid aspirated with microcapillaries was subjected to a fluorometric plasmin assay using the 7-amido-4-trifluoromethylcoumarin derivate of the tripeptide H-D-Val-Leu-Lys as substrate. RESULTS Tear Fluid flow, plasmin activity, and flow-corrected plasmin excretion rate in Tears (plasmin flux) were determined preoperatively and 1, 2, and 7 days after PRK. The preoperative Tear Fluid flow was 6.55 microliters/min (median; range, 1.8 to 21.8 microliters/min), plasmin activity was 1.29 IU/l (median; range, 0.6 to 6.9 IU/l), and the excretion of plasmin in Tears was 11.7 microIU/min (median; range, 1.6 to 41.5 microIU). A statistically significant decrease in Tear Fluid plasmin activity was found during the follow-up period on the first (0.6 IU/l; range, 0.6 to 1.7 IU/l, P 0.05), respectively. CONCLUSION The marked elevation of Tear Fluid flow coincided with the persistence of an epithelial defect. However, because of the acceleration of Tear Fluid flow, proteolytic activity due to plasmin (IU/l) actually decreases. Consequently, the increased excretion of plasmin in Tears (plasmin flux) does not lead to highly elevated plasmin activity, which could inhibit wound healing. It seems to be a natural healing response because all corneas were epithelialized normally by or on day 3.
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A rapid fluorometric assay for Tear Fluid plasmin activity.
Cornea, 1994Co-Authors: Timo Tervo, Ahti Tarkkanen, Tuula Virtanen, Niina Honkanen, Van Setten Gb, Matti HärkönenAbstract:A rapid (5- to 10-min), sensitive (detection limit 0.6 IU/L), and moderately specific fluorometric plasmin assay for small volume Tear Fluid samples was developed. Addition of albumin (up to 0.1% final concentration) to the assay buffer improved the sensitivity of the test so that plasmin activity in healthy controls could be detected. pH in the reaction buffer was 8.0, Michaelis-Menten constant for the substrate, H-D-Val-Leu-Lys.7-amido-4-methyl-coumarin (AMC), was 0.28 mM, and final substrate concentration in the reaction buffer was 1 mM. Intra- and interassay imprecisions were 1.6 and 4.4%, respectively at a plasmin level of 10 IU/L. Tear Fluid flow was significantly higher in the patients than in the healthy controls, and this dilatory effect must be considered when using plasmin determination for diagnostic purposes. This effect was counteracted by correcting the plasmin activity values by Tear Fluid flow. Plasmin flux is plasmin activity (microIU) secreted in units of time (min). This parameter showed highly significant differences between the patients and controls. All patients with microbial keratitis, corrosive trauma, ocular trauma, herpetic infection, and other diseases showed highly significant elevation of plasmin flux compared with controls. The highest plasmin flux values (several hundredfold that of controls) were recorded in patients with severe corneal ulcers. Few patient samples showed some involvement of other proteases, which were not inhibited by aprotinin.
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Elevation of Tear Fluid Plasmin Activity of Contact Lens Wearers Studied with a Rapid Fluorometric Assay
Cornea, 1994Co-Authors: Tuula Virtanen, Ahti Tarkkanen, Matti Härkönen, Niina Honkanen, Timo TervoAbstract:Tear Fluid plasmin activities were measured by a fluorometric assay based on a lyophilized kit with the 7-amido-4-trifluoromethylcoumarin derivative of the tripeptidyl H-D-Val-Leu-Lys as substrate. The rapid, sensitive method can detect proteolytic activity in small volume Tear Fluid samples. Plasmin activity levels (IU/L) measured from the samples were corrected with Tear Fluid flows (microliters/min), yielding a parameter called plasmin flux (microIU/min). Correction is important when patients show Tearing due to irritation. Tear Fluid samples were collected from 32 asymptomatic contact lens (CL) wearers and 27 controls. Plasmin activity values (2.7 +/- 0.3 IU/L) of CL wearers were higher (p < 0.00006) than those of the controls (1.6-0.1). Mean plasmin flow was 12.6 +/- 1.5 microliters/min for CL wearers and higher for controls (6.8 +/- 0.5 microliters/min). The difference was not significant (p = 0.063). Plasmin flux values of CL wearers (30.0 +/- 4.1 microIU/min) were conspicuously higher than those of controls (10.2 +/- 0.7 microIU/min, p < 0.00006). We conclude that elevated Tear Fluid proteolytic activity may be related to pathological changes associated with CL wear.
Matti Härkönen - One of the best experts on this subject based on the ideXlab platform.
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Tear Fluid plasmin activity of dry eye patients with Sjögren's syndrome.
Acta ophthalmologica Scandinavica, 2009Co-Authors: Tuula Virtanen, Matti Härkönen, Yrjö T. Konttinen, Niina Honkanen, Timo TervoAbstract:Thirty-two eyes of 16 patients with verified Sjogren's syndrome were examined for clinical signs of dry eye. Tear Fluid samples were collected for plasmin assay. Ophthalmologic examinations included estimation of conjunctival or corneal discharge, filament formation and presence of conjunctival or corneal epithelial defects, assessment of Tear meniscus height and measurement of Tear Fluid break-up time, Schirmer test, and fluorescein and Rose-Bengal staining graded by the van Bijsterveld score. Tear Fluid plasmin activity (IU/l) was determined by a fluorometric assay and Tear Fluid flow (microl/min) was measured for calculation of Tear Fluid plasmin activity release (microIU/min). All patients had relatively dry eyes; the mean Schirmer test value was 5.7 +/- 0.5 mm/5 min. The mean Tear Fluid break-up time was also low, 7.7 +/- 0.5 s. The mean Bijsterveld score value was 2.5 +/- 0.5. Because collection of Tear Fluid by microcapillaries for the plasmin assay was difficult due to the low Tear Fluid flow rate, it was necessary to drop 20 microl of balanced salt solution topically on the cornea to aspirate a Tear Fluid sample. Despite this, the mean Tear Fluid plasmin activity was higher than in control individuals (7.75 +/- 1.51 IU/l vs. 0.73, range 0.64-0.80 IU/l). On the basis of these findings we conclude that elevated Tear Fluid proteolytic activity may play a role in the pathology of dry eye/ocular surface disease.
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Tear Fluid Plasmin Activity After Excimer Laser Photorefractive Keratectomy
Investigative ophthalmology & visual science, 1994Co-Authors: Timo Tervo, Tuula Virtanen, N. Honkanen, Matti Härkönen, Ahti TarkkanenAbstract:PURPOSE Elevated Tear Fluid plasmin activity may correlate with delayed healing of corneal wounds. The present study was performed to establish the Tear Fluid plasmin activity after photorefractive keratoablation (PRK). METHODS Tear Fluid aspirated with microcapillaries was subjected to a fluorometric plasmin assay using the 7-amido-4-trifluoromethylcoumarin derivate of the tripeptide H-D-Val-Leu-Lys as substrate. RESULTS Tear Fluid flow, plasmin activity, and flow-corrected plasmin excretion rate in Tears (plasmin flux) were determined preoperatively and 1, 2, and 7 days after PRK. The preoperative Tear Fluid flow was 6.55 microliters/min (median; range, 1.8 to 21.8 microliters/min), plasmin activity was 1.29 IU/l (median; range, 0.6 to 6.9 IU/l), and the excretion of plasmin in Tears was 11.7 microIU/min (median; range, 1.6 to 41.5 microIU). A statistically significant decrease in Tear Fluid plasmin activity was found during the follow-up period on the first (0.6 IU/l; range, 0.6 to 1.7 IU/l, P 0.05), respectively. CONCLUSION The marked elevation of Tear Fluid flow coincided with the persistence of an epithelial defect. However, because of the acceleration of Tear Fluid flow, proteolytic activity due to plasmin (IU/l) actually decreases. Consequently, the increased excretion of plasmin in Tears (plasmin flux) does not lead to highly elevated plasmin activity, which could inhibit wound healing. It seems to be a natural healing response because all corneas were epithelialized normally by or on day 3.
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A rapid fluorometric assay for Tear Fluid plasmin activity.
Cornea, 1994Co-Authors: Timo Tervo, Ahti Tarkkanen, Tuula Virtanen, Niina Honkanen, Van Setten Gb, Matti HärkönenAbstract:A rapid (5- to 10-min), sensitive (detection limit 0.6 IU/L), and moderately specific fluorometric plasmin assay for small volume Tear Fluid samples was developed. Addition of albumin (up to 0.1% final concentration) to the assay buffer improved the sensitivity of the test so that plasmin activity in healthy controls could be detected. pH in the reaction buffer was 8.0, Michaelis-Menten constant for the substrate, H-D-Val-Leu-Lys.7-amido-4-methyl-coumarin (AMC), was 0.28 mM, and final substrate concentration in the reaction buffer was 1 mM. Intra- and interassay imprecisions were 1.6 and 4.4%, respectively at a plasmin level of 10 IU/L. Tear Fluid flow was significantly higher in the patients than in the healthy controls, and this dilatory effect must be considered when using plasmin determination for diagnostic purposes. This effect was counteracted by correcting the plasmin activity values by Tear Fluid flow. Plasmin flux is plasmin activity (microIU) secreted in units of time (min). This parameter showed highly significant differences between the patients and controls. All patients with microbial keratitis, corrosive trauma, ocular trauma, herpetic infection, and other diseases showed highly significant elevation of plasmin flux compared with controls. The highest plasmin flux values (several hundredfold that of controls) were recorded in patients with severe corneal ulcers. Few patient samples showed some involvement of other proteases, which were not inhibited by aprotinin.
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Elevation of Tear Fluid Plasmin Activity of Contact Lens Wearers Studied with a Rapid Fluorometric Assay
Cornea, 1994Co-Authors: Tuula Virtanen, Ahti Tarkkanen, Matti Härkönen, Niina Honkanen, Timo TervoAbstract:Tear Fluid plasmin activities were measured by a fluorometric assay based on a lyophilized kit with the 7-amido-4-trifluoromethylcoumarin derivative of the tripeptidyl H-D-Val-Leu-Lys as substrate. The rapid, sensitive method can detect proteolytic activity in small volume Tear Fluid samples. Plasmin activity levels (IU/L) measured from the samples were corrected with Tear Fluid flows (microliters/min), yielding a parameter called plasmin flux (microIU/min). Correction is important when patients show Tearing due to irritation. Tear Fluid samples were collected from 32 asymptomatic contact lens (CL) wearers and 27 controls. Plasmin activity values (2.7 +/- 0.3 IU/L) of CL wearers were higher (p < 0.00006) than those of the controls (1.6-0.1). Mean plasmin flow was 12.6 +/- 1.5 microliters/min for CL wearers and higher for controls (6.8 +/- 0.5 microliters/min). The difference was not significant (p = 0.063). Plasmin flux values of CL wearers (30.0 +/- 4.1 microIU/min) were conspicuously higher than those of controls (10.2 +/- 0.7 microIU/min, p < 0.00006). We conclude that elevated Tear Fluid proteolytic activity may be related to pathological changes associated with CL wear.
Ju Prause - One of the best experts on this subject based on the ideXlab platform.
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Serum albumin, serum antiproteases and polymorphonuclear leucocyte neutral collagenolytic protease in the Tear Fluid of normal healthy persons.
Acta ophthalmologica, 2009Co-Authors: Ju PrauseAbstract:Using a micro-electroimmune assay and a 'non-reflex stimulating' method to collect normal Tear Fluid, the concentration of the serum proteins albumin (S-A), alfa-1-antitrypsin (alpha 1A), alfa-1-antichymotrypsin (alpha 1X) and alfa-2-macroglobulin (alpha 1M) was determined in the Tear Fluid of 53 normal persons. In addition, the Tear Fluid was tested for the content of polymorphonuclear leucocyte neutral collagenolytic protease (PML-c-ase). PML-c-ase and alpha 1X could not be detected in any Tear samples. The concentrations of S-A, alpha 1A and alpha 1M were constant over time, and showed no variation with sex, age or between the right and left eyes. There was no correlation between the concentration levels of the detected proteins in the Tear Fluid and correlation between Tear Fluid levels and corresponding serum concentration levels of the proteins could not be shown.
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serum albumin serum antiproteases and polymorphonuclear leucocyte neutral collagenolytic protease in the Tear Fluid of patients with corneal ulcers
Acta Ophthalmologica, 2009Co-Authors: Ju PrauseAbstract:Using a micro-electroimmune assay, the concentration of polymorphonuclear leucocyte neutral collagenolytic protease, serum-albumin, alpha-1-antitrypsin and alpha-2-macroglobulin were measured in the Tear Fluid from 18 eyes of 16 patients with severe, melting corneal ulcers. By this method, PML-c-ase was the first time detected in Tear Fluid. All proteins normalized during healing of the ulcer. The findings are indicative of an important role for PML-proteases in the degradation of the corneal stroma, and of a regulative effect of the serum antiproteases leaking into the Tear Fluid from inflamed conjunctival vessels.
Timo Sorsa - One of the best experts on this subject based on the ideXlab platform.
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elevated expression and activation of matrix metalloproteinase 8 in Tear Fluid in atopic blepharoconjunctivitis
Cornea, 2008Co-Authors: Marko Määttä, Osmo Kari, Taina Tervahartiala, Sirje Peltonen, Marjatta Kari, Matti Saari, J Wahlgren, P Rytila, Timo SorsaAbstract:PURPOSE: Matrix metalloproteinase 8 (MMP-8) is an effective collagenolytic enzyme that is associated with many ocular inflammatory diseases, such as uveitis, keratitis, and ocular rosacea. We studied the Tear Fluid concentration and activation of MMP-8 in atopic blepharoconjunctivitis (ABC) and the presence of the enzyme in conjunctival inflammatory cells in vivo. METHODS: Tear Fluid samples were collected from 26 patients with ABC and 26 healthy controls. MMP-8 concentrations were determined by immunofluorometric assay, and its molecular forms and degrees of activation were studied by Western blotting. Conjunctival brush cytology samples from patients with ABC were used for MMP-8 immunocytochemistry. RESULTS: : The mean MMP-8 concentration was statistically significantly higher among the patients with ABC (545.6 +/- 879.3 microg/L) than among the healthy controls (50.4 +/- 62.3 microg/L, P = 0.0001). There was a statistically significant correlation between neutrophils detected in brush cytology and Tear Fluid MMP-8 (P = 0.032, r = 0.47). Both the control and ABC Tear Fluid samples contained predominantly the larger (60-80 kDa), highly glycosylated polymorphonuclear leukocyte-type MMP-8 isoform, as identified by Western blotting, but neither was found to contain the mesenchymal-type isoform. The active enzyme was in practice present only in the ABC samples. Immunostainings show the MMP-8 protein to be present in all the main inflammatory cell types within the conjunctiva. CONCLUSIONS: : 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.
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Tear Fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline
Graefe's Archive for Clinical and Experimental Ophthalmology, 2006Co-Authors: Marko Määttä, Osmo Kari, Taina Tervahartiala, Sirje Peltonen, Marjatta Kari, Matti Saari, Timo SorsaAbstract:Background Ocular rosacea (OcR) is a chronic inflammatory disease especially affecting lid margins. Previous studies have shown that it is accompanied by increased levels and activation of Tear Fluid gelatinases. Matrix metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly elevated in many inflammatory conditions. Therefore we studied here whether MMP-8 concentration and activation in Tear Fluid are increased also in OcR, and if an oral doxycycline regimen could rectify the situation. Methods Tear Fluid samples were collected from 22 OcR patients and 22 healthy controls. The OcR patients were then treated with an oral doxycycline regimen for 8 weeks and Tear Fluid samples collected again after 4 and 8 weeks. Conjunctival brush cytology and patients’ subjective symptoms were scored. MMP-8 concentrations in the Tear Fluid were assessed by immunofluorometric assay and the molecular forms and isoenzyme expression of MMP-8 were studied by Western immunoblotting. Results The mean MMP-8 concentration was statistically significantly higher in OcR (156.8±207.4 μg/ml) than in the normal subjects (53.5±66.7 μg/ml) ( P =0.036), but decreased to 79.2±141.6 μg/l and 53.6±75.2 μg/l after 4 and 8 weeks doxycycline treatment, respectively. There was a statistically significant difference between the untreated OcR and the MMP-8 results after 4 or 8 weeks of oral doxycycline ( P =0.041 and 0.069, respectively) and the OcR patients experienced statistically significant relief of their subjective symptoms ( P =0.0001) after the doxycycline regimen. Both the normal and OcR Tear Fluid contained the larger, 60-80 kDa highly- glycosylated polymorphonuclear leukocyte-type MMP-8 isoform in Western immunoblotting, but not the 45–55 kDa less glycosylated mesenchymal-type isoform. MMP-8 activation was in practice present only in the OcR samples, and was inhibited by oral doxycycline. Conclusions MMP-8 concentration and activation degree in Tear Fluid are increased in OcR, probably reflecting increased inflammatory activity. Doxycycline effectively reduces these pathologically excessive levels and activation of MMP-8, and relieves patients’ subjective symptoms.
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Tear Fluid levels of mmp 8 are elevated in ocular rosacea treatment effect of oral doxycycline
Graefes Archive for Clinical and Experimental Ophthalmology, 2006Co-Authors: Marko Määttä, Osmo Kari, Taina Tervahartiala, Sirje Peltonen, Marjatta Kari, Matti Saari, Timo SorsaAbstract:Background Ocular rosacea (OcR) is a chronic inflammatory disease especially affecting lid margins. Previous studies have shown that it is accompanied by increased levels and activation of Tear Fluid gelatinases. Matrix metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly elevated in many inflammatory conditions. Therefore we studied here whether MMP-8 concentration and activation in Tear Fluid are increased also in OcR, and if an oral doxycycline regimen could rectify the situation.
