Tear fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline

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

doi:10.1007/s00417-005-0212-3

Cited by 80 publications

(48 citation statements)

References 41 publications

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“…An elevated concentration of interleukin-1a and b and a greater activity of gelatinase B (metalloproteinase -9) and colagenase-2 (MMP-8) have been found in tear fluids of patients with ocular rosacea (19)(20)(21)(22) . Doxycycline, used in the treatment of cutaneous and ocular rosacea, decreases both MMP-8 and MMP-9 activity (21,22) . Tumor necrosis factor (TNF-alfa) was also elevated in rosacea (23) .…”

Section: Etiology and Pathophysiologymentioning

confidence: 99%

Ocular rosacea: a review

Vieira¹,

Höfling-Lima²,

Mannis³

2012

Arq. Bras. Oftalmol.

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Section: Etiology and Pathophysiologymentioning

confidence: 99%

Ocular rosacea: a review

Vieira¹,

Höfling-Lima²,

Mannis³

2012

Arq. Bras. Oftalmol.

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“…There is strong evidence for the role of KLK5, which can activate signaling pathways leading to the production of inflammatory mediators and cytokines, including several matrix metalloproteases [15]. Ocular surface inflammation in rosacea has also been related to increased levels of IL-1α, MMP-8, and gelatinase-B (proMMP-9) activity in the tears of these patients [3, 4, 9]. In addition, gelatinase-B activity correlates with a delayed tear clearance and tear fluid concentration of IL-1α, which increases the production and activity of certain enzymes of the MMP family, including MMP-8 and MMP-9 [4].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, gelatinase-B activity correlates with a delayed tear clearance and tear fluid concentration of IL-1α, which increases the production and activity of certain enzymes of the MMP family, including MMP-8 and MMP-9 [4]. These enzymes degrade the extracellular matrix and may contribute to the development of recurrent corneal epithelial erosions, corneal vascularization, persistent epithelial defects, and ulceration [6, 9, 11]. Moreover, inflammatory factors including IL-1 may alter the sensory neural threshold, reducing ocular sensation and decreasing the stimulation reflex to the lacrimal glands, which further decreases tear clearance [16, 17].…”

Section: Discussionmentioning

confidence: 99%

“…These proinflammatory cytokines may be used as biomarkers for disease activity and to monitor therapeutic response [4]. There is scant evidence on the behavior of these cytokines on the tear film of ocular rosacea patients, particularly the therapeutic response to tetracycline and macrolides [8, 9]. The objective of the present study was to determine the correlation of the tear levels of IL-1α and MMP-9 in patients with active ocular rosacea compared to normal controls and after conventional treatment with systemic azithromycin or doxycycline.…”

Section: Introductionmentioning

confidence: 99%

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IL-1α and MMP-9 Tear Levels of Patients with Active Ocular Rosacea before and after Treatment with Systemic Azithromycin or Doxycycline

et al. 2018

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Aims: The purpose of this paper was to determine the lacrimal concentration of IL-1α and MMP-9 in patients with active ocular rosacea before and after systemic treatment with azithromycin or doxycycline. Methods: After 4 weeks of therapy with azithromycin (500 mg/day, 3 days a week PO) or doxycycline (200 mg/day PO), lacrimal samples were analyzed using an enzyme-linked immunosorbent assay multiplex. Results: There was a significant difference between baseline IL-1α (37.9 pg/mL) and MMP-9 (26.7 ng/mL) in rosacea eyes compared to controls (0.001 pg/mL for IL-1α and 0.2 ng/mL for MMP-9) (p < 0.001). IL-1α decreased from 47.0 pg/mL before azithromycin to 23.5 pg/mL after treatment (p = 0.024), but not after doxycycline therapy. On the contrary, baseline MMP-9 tear levels (10.28 ng/mL) decreased after treatment (8.36 pg/mL) with doxycycline (p = 0.054) but not with azithromycin. There was a strong clinical correlation of higher baseline IL-1α tear levels between patients who responded to doxycycline therapy and those who failed (p = 0.043). Patients unresponsive to azithromycin had significantly higher baseline MMP-9 levels than those with doxycycline (p = 0.040). Conclusions: While IL-1α levels decreased after azithromycin therapy, MMP-9 did so after doxycycline treatment. Baseline cytokine tear levels tend to be markedly elevated in patients with antibiotic failure, suggesting their potential role as therapeutic biomarkers for the disease.

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“…org/wiki/Prostatitis), sinusitis, syphilis, chlamydia (http://en. wikipedia.org/wiki/Chlamydia), pelvic inflammatory disease, acne (http://en.wikipedia.org/wiki/Acne_vulgaris), and rosacea (http://en.wikipedia.org/wiki/Rosacea) (1,2) and in the treatment and prophylaxis of Bacillus anthracis and malaria (3). DOX was shown to be effective against several other pathogens causing a number of diseases and, since it is at sub-antimicrobial doses an inhibitor of matrix metalloproteinases, DOX can be proposed for a number of purposes (4).…”

Section: Introductionmentioning

confidence: 99%

Formulation and Release Behavior of Doxycycline–Alginate Hydrogel Microparticles Embedded into Pluronic F127 Thermogels as a Potential New Vehicle for Doxycycline Intradermal Sustained Delivery

2010

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Abstract. The aim of this work was the formulation and characterization of alginate (ALG)-doxycycline (DOX) hydrogel microparticles (MPs) embedded into Pluronic F127 thermogel for DOX intradermal sustained delivery. ALG-DOX MPs were formed by adding a solution of the drug into a 1.5% polymer solution while stirring. The MPs were cross-linked by dispersion into a 1.2% CaCl 2 solution. Free MPs were characterized in terms of size, drug content, and release behavior by HPLC and UV-vis. DOX and hydrogel MPs were embedded into PF127, PF127-HPMC, and PF127-Methocel thermogels. The thermogels were characterized in terms of gelling time, morphology, and release behavior. A target release period of 4-7 days was considered optimal. The hydrogel MPs were about 20 µm in size with 90% of the population <59 µm. Drug content was about 35% (w/w). DOX released rapidly from the MPs, 90% within 2 days. An expected faster release was observed for free DOX from the thermogels with 80-90% of drug released after 3.5-4 h even in the presence of 1% HPMC or Methocel. The release was sustained after embedding the MPs into PF127 and PF127-HPMC thermogels. In particular, the PF127-HPMC thermogel showed an almost linear release, reaching 80% after 3 days and 90% up to 6 days. Although a further characterization and formulation assessment is required to optimize MP characteristics, ALG/DOX-loaded hydrogel MPs, when embedded into a PF127-HPMC thermogel, show a potential for achieving a 7-day sustained release formulation for DOX intradermal delivery.

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Tear fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline

Abstract: 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.

Cited by 80 publications

References 41 publications

Ocular rosacea: a review

Ocular rosacea: a review

IL-1α and MMP-9 Tear Levels of Patients with Active Ocular Rosacea before and after Treatment with Systemic Azithromycin or Doxycycline

Formulation and Release Behavior of Doxycycline–Alginate Hydrogel Microparticles Embedded into Pluronic F127 Thermogels as a Potential New Vehicle for Doxycycline Intradermal Sustained Delivery

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