Tear Matrix Metalloproteinase Research Articles

Ocular surface parameter changes in the untreated fellow eye after unilateral cataract surgery with short-term administration of anti-inflammatory eye drops

This study aimed to investigate the changes in clinical parameters of dry eye disease and meibomian gland dysfunction in both the operated and untreated fellow eyes of patients who underwent unilateral cataract surgery with the short-term administration of anti-inflammatory eye drops in the surgical eye. The medical charts of 57 consecutive patients who underwent unilateral cataract surgery and received 1% prednisolone acetate and non-steroidal anti-inflammatory drug (NSAID, 0.1% bromfenac sodium) eye drops were reviewed. The preoperative ocular surface disease index questionnaire score (38.9 ± 20.5) decreased significantly to 15.2 ± 16.4 at post-surgical 1 week and further to 12.8 ± 11.4 after 1 month. Although meibum quality grade increased and corneal sensitivity decreased at 1 week in operated eyes, corneal erosion scores and Sjogren’s International Collaborative Clinical Alliance ocular staining scores even improved over a month in the untreated fellow eyes. The tear matrix metalloproteinase (MMP)-9 grade decreased in both operated eyes and untreated fellow eyes after 1 month from surgery. In conclusion, the short-term topical anti-inflammatory treatment using steroid and NSAID eye drops in the operated eye after cataract surgery decreased subjective ocular surface discomfort and improved ocular surface staining scores and tear MMP-9 expression in the untreated fellow eyes.

Ocular Surface Disease Related to the Inflammatory and Non-Inflammatory Phases of Thyroid Eye Disease.

This study evaluated the ocular surface disease (OSD), especially dry eye disease (DED) parameters by combining qualitative and quantitative tools, including tear matrix metalloproteinase 9 (MMP-9), in patients with Graves' disease (GD) with and without Thyroid eye disease (TED). A total of 17 active TED, 16 inactive TED, 16 GD without ophthalmopathy, and 16 healthy controls were included. All patients were assessed with CAS, ophthalmometry, qualitative tear MMP-9, Ocular Surface Disease Index (OSDI), ocular surface staining, Schirmer test, meibography, tear meniscus height, conjunctival hyperemia, and non-invasive tear film break-up time. Patients were classified into three subtypes of DED: aqueous tear deficiency, meibomian gland dysfunction (MGD) and mixed dry eye. Inactive TED was shown to be an associated factor with DED (odds ratio 14, confidence interval 2.24-87.24, p=0.0047), and presented more DED than healthy controls (87.5% versus 33.3%, p=0.0113). MGD was also more prevalent among these subjects than in healthy control (62.5% versus 6.7%; p=0.0273). No significant differences were found in other ophthalmological parameters, except for more intense conjunctival redness among active TED than GD without ophthalmopathy (p=0.0214). Qualitative MMP-9 test was more frequently positive in both eyes among active TED than in other groups (p < 0.0001). Patients with GD were symptomatic and presented a high prevalence of ocular surface changes and DED, particularly the subgroup with inactive TED. Tear MMP-9 detection was associated with active TED suggesting a relationship between ocular surface changes and the initial inflammatory phase of ophthalmopathy.

Dichotomous versus 5-scale grading system for the interpretation of the point-of-care immunoassay for tear matrix metalloproteinase-9 in dry eye

In this study, we compared the dichotomous and 5-scale grading systems for point-of-care immunoassay of tear matrix metalloproteinase (MMP)-9 in dry eye disease (DED) patients and identified the optimal dichotomous system to correlate with DED parameters. We included 167 DED patients without primary Sjogren's syndrome (pSS) (Non-SS DED) and 70 DED patients with pSS (SS DED). We graded MMP-9 expression in InflammaDry® (Quidel, San Diego, CA, USA) using a 5-scale grading system and dichotomous grading systems with four different cut-off grades (D1 to D4 systems). The only DED parameter that showed a significant correlation with the 5-scale grading method was tear osmolarity (Tosm). In both groups, subjects with positive MMP-9 had lower tear secretion and higher Tosm than those with negative MMP-9 according to the D2 dichotomous system. Tosm determined D2 positivity at cutoffs > 340.5 and > 317.5 mOsm/L in the Non-SS DED and SS DED groups, respectively. Tear secretion < 10.5 mm or tear break-up time < 5.5 s stratified D2 positivity in the Non-SS DED group. In conclusion, the dichotomous grading system of InflammaDry reflects ocular surface indices better than the 5-scale grading system and may be more practical in real clinical circumstances.

A preliminary study on the tear matrix metalloproteinase 9 point-of-care assay using a domestic kit

Objective: To compare the point-of-care assays for tear matrix metalloproteinase 9 (MMP-9) using domestic and InflammaDry kits, and to evaluate the feasibility of diagnosing dry eye with the domestic kit. Methods: It was a cross-sectional study. Thirty dry eye patients and 30 age-and sex-matched normal volunteers were continuously enrolled in this cross-sectional study from June 2022 to July 2022. Both domestic and InflammaDry kits were used to detect the tear MMP-9 levels. The positive rates were recorded for qualitative analysis, and the gray ratios of bands (the gray value of detection bands to that of control bands) were collected for quantitative analysis. The correlations of MMP-9 levels with age, ocular surface disease index, fluorescence tear break-up time, tear meniscus height, Schirmer's Ⅰ test score, corneal fluorescein staining score, and meibomian gland dropout were analyzed. The Mann-Whitney U test, paired Chi-square test, Kappa test, and Spearman's correlation coefficient were used for statistical analysis. Results: There were 14 males and 16 females (30 eyes) in the control group, and their age was (39.37±19.55) years. In the dry eye group, 11 males and 19 females (30 eyes), aged (46.87±17.85) years, had moderate to severe dry eye. The positive rates of MMP-9 in tear fluid were significantly different between dry eye patients (InflammaDry: 86.67%; domestic kit: 70.00%) and controls (InflammaDry: 16.67%, P<0.001; domestic kit: 6.67%, P<0.001). Although the sensitivity of the domestic kit was lower than that of the InflammaDry kit (70.0% vs. 86.7%, P=0.001), the specificity was higher (93.3% vs. 83.3%, P=0.001). In dry eye patients, the positive coincidence rate was 80.7% (21/26), the negative coincidence rate was 100% (4/4), and the total coincidence rate was 83.3% (25/30), with no significant difference between the two kits (McNemar test: χ2=3.20, P>0.05), and the results of both kits were consistent (Kappa=0.53, P=0.001). The Spearman's correlation coefficient showed the gray ratios using both kits were positively correlated with the corneal fluorescein staining score (InflammaDry: ρ=0.48, P<0.05; domestic kit: ρ=0.52, P=0.003). Conclusion: The performances of the domestic and InflammaDry kits are consistent in the point-of-care assay for tear MMP-9, and the domestic kit has lower sensitivity but higher specificity.

Tear matrix metalloproteinase-9 levels may help to follow a ocular surface injury in lagophthalmic eyes.

The preocular tear film is critically important for maintaining healthy ocular surface. In lagophthalmos, increased evaporation and tear film instability can occur. The level of tear matrix metalloproteinase 9 (MMP-9) is considered as a possible marker of ocular surface damage and inflammation. The aim of this study was to evaluate the possible usefulness of measuring tear film levels of MMP-9 in patients with lagophthalmos. Sixteen adult patients with unilateral lagophthalmos due to cerebellopontine angle mass surgery were included. Basic clinical examination including tear film osmolarity, degree of lagophthalmos, ocular surface sensitivity testing, corneal fluorescein staining, and tear break-up time (TBUT) were performed. Furthermore, tear MMP-9 quantification was performed and the values from lagophthalmic and contralateral healthy eye were compared. Possible correlations between tear MMP-9 levels and other parameters were analyzed. The Oxford score was higher in lagophthalmic eyes in comparison to healthy eyes. TBUT and corneal sensitivity were lower in lagophthalmic eyes. There was no difference in osmolarity between the two groups. Tear MMP-9 values were higher in lagophthalmic eyes. A higher MMP-9 value was associated with an increase in ocular surface fluorescein staining and a decrease of TBUT in lagophthalmic eyes. Tear MMP-9 may be used for monitoring ocular surface damage, contribute to early detection of inflammation progression and facilitate treatment adjustments.

Matrix metalloproteinase 9 is associated with conjunctival microbiota culture positivity in Korean patients with chronic Stevens-Johnson syndrome

BackgroundStevens-Johnson syndrome (SJS) is an abnormal immune-response causing extensive exfoliation of the mucocutaneous tissue including conjunctiva. While several factors are associated with the alteration of conjunctival microbiota, the conjunctiva of SJS patients are found to harbor a different microbiota compared to healthy subjects. We investigated the conjunctival microbiota of Korean SJS patients, and identified factors associated with the conjunctival microbiota and its positive culture.MethodsMedical records were retrospectively reviewed in 30 chronic SJS patients who had undergone conjunctival swab culture sampling. Demographic factors, chronic ocular surface complications score (COCS), tear break-up time (TBUT), tear secretion, tear matrix metalloproteinase 9 (MMP9), and results of conjunctival swab culture were assessed.ResultsPositive culture was seen in 58.1%. Gram positive bacteria was most commonly isolated, among which Coagulase-negative Staphylococci (45.5%) and Corynebacterium species (40.9%) were predominantly observed. Tear MMP9 positivity was observed significantly more in the positive culture group (100%) compared to the negative culture group (70%) (P = 0.041). Topical cyclosporine and corticosteroid were not associated with repetitive positive cultures. No significant differences in COCS, TBUT, and tear secretion were found between culture-positive and culture-negative groups.ConclusionOur study suggests that tear MMP9 positivity may be related with the presence of an abnormal ocular surface microbiota in chronic SJS patients.

Association of tear matrix metalloproteinase 9 immunoassay with signs and symptoms of dry eye disease: A cross-sectional study using qualitative, semiquantitative, and quantitative strategies

PurposeThis study aimed to analyze the association of tear matrix metalloproteinase 9 (MMP-9) immunoassay with the severity of dry eye (DE) signs and symptoms through qualitative, semiquantitative, and quantitative evaluations of immunoassay band.Materials and methodsThis cross-sectional study enrolled 320 eyes of 320 patients. The clinical signs of DE were assessed using the Ocular Surface Disorder Index (OSDI) score, visual analogue scale (VAS), tear breakup time (tBUT), tear volume evaluation by tear meniscometry, and staining scores of the cornea and conjunctiva by the Oxford grading scheme. The tear MMP-9 immunoassay results were interpreted using qualitative (positive or negative), semi-quantitative (reagent band density on a four-point scale: 0 = negative; 1 = weakly positive; 2 = moderately positive; 3 = strongly positive), and quantitative (ratio of reagent band density to control band density) indicators.ResultsPositive MMP-9 immunoassay results were significantly related to shorter tBUT, tBUT ≤3 seconds, higher corneal staining score, corneal staining score ≥2, and conjunctival staining score ≥2. The semi-quantitative results of the MMP-9 immunoassay were positively correlated with higher corneal staining score (r = 0.122, p = 0.029) and negatively correlated with tBUT (r = -0.125, p = 0.025). However, in the quantitative analysis, none of the DE signs or symptoms were correlated to the band density of the MMP-9 immunoassay.ConclusionsThe positive MMP-9 immunoassay results were related to the severity of ocular signs of DE. However, using quantitative measures of the MMP-9 immunoassay to assess the clinical severity of DE requires further investigation.

Assessment of reliability and validity of the 5-scale grading system of the point-of-care immunoassay for tear matrix metalloproteinase-9

We evaluated the reliability and validity of the 5-scale grading system to interpret the point-of-care immunoassay for tear matrix metalloproteinase (MMP)-9. Six observers graded red bands of photographs of the readout window in MMP-9 immunoassay kit (InflammaDry) two times with 2-week interval based on the 5-scale grading system (i.e. grade 0–4). Interobserver and intraobserver reliability were evaluated using intraclass correlation coefficients. The interobserver agreements were analyzed according to the severity of tear MMP-9 expression. To validate the system, a concentration calibration curve was made using MMP-9 solutions with reference concentrations, then the distribution of MMP-9 concentrations was analyzed according to the 5-scale grading system. Both intraobserver and interobserver reliability was excellent. The readout grades were significantly correlated with the quantified colorimetric densities. The interobserver variance of readout grades had no correlation with the severity of the measured densities. The band density continued to increase up to a maximal concentration (i.e. 5000 ng/mL) according to the calibration curve. The difference of grades reflected the change of MMP-9 concentrations sensitively, especially between grade 2 and 4. Together, our data indicate that the subjective 5-scale grading system in the point-of-care MMP-9 immunoassay is an easy and reliable method with acceptable accuracy.

Short-term Changes in the Tear Matrix Metalloproteinase 9 Level and Ocular Surface Discomfort after Cataract Surgery

Short-term Changes in the Tear Matrix Metalloproteinase 9 Level and Ocular Surface Discomfort after Cataract Surgery

Short-Term Therapeutic Effects of Topical Corticosteroids on Refractory Dry Eye Disease: Clinical Usefulness of Matrix Metalloproteinase 9 Testing as a Response Prediction Marker.

PurposeTo compare the short-term therapeutic effects of topical corticosteroids in patients with refractory dry eye disease (DED) according to the tear matrix metalloproteinase 9 (MMP-9) point-of-care positivity.MethodsThis study was conducted on 137 patients who were referred from other eye clinics, complaining of irresponsive DED or acute DED flares despite routine treatment with topical cyclosporin or diquafosol. The patients received treatment with topical corticosteroids for 1 month. DED was evaluated by SANDE (Symptom Assessment in Dry Eye) questionnaire, tear film breakup time, ocular surface staining score, and meibomian gland dysfunction stage. The InflammaDry MMP-9 immunoassay was conducted in more symptomatic eyes of all patients. The changes in the subjective symptoms were additionally surveyed as symptom improvement score.ResultsThe mean age of the patients was 57.8±13.4 years, and the tear MMP-9 positivity was 73.0%. Topical corticosteroids treatment showed significant improvement of symptoms and signs in the patients with refractory DED irrespective of the positivity of MMP-9 (each p<0.001). The changes in SANDE score and OSS, and symptom improvement score were higher in the MMP-9 positive group than in the MMP-9 negative group (p=0.002/0.010/0.011). The overall rates of subjective symptoms improvement and SANDE reduction were 73.0% and 90.6% after topical corticosteroids treatment, respectively.ConclusionShort-term topical corticosteroids had excellent therapeutic effects in patients with refractory DED or acute DED flares, irrespective of the tear MMP-9 level. Tear MMP-9 positivity may serve as a reliable response predictor of topical corticosteroids treatment in DED.

Efficacy of topical cyclosporine 0.05% and osmoprotective lubricating eye drops in treating dry eye disease and inflammation.

Purpose:To evaluate the effect of topical cyclosporine 0.05% and osmoprotective lubricating eye drops on patients with dry eye disease (DED) with inflammation as measured by raised tear matrix metalloproteinases (MMP-9).Methods:This prospective study included 106 eyes of 53 patients diagnosed with DED based on any of the following DED criteria (Ocular Surface Disease Index [OSDI] score >12, tear film breakup time [TBUT] <10 s, Schirmer’s I test result <10 mm/5 min, ocular surface staining). Ocular surface inflammation was assessed by assessing MMP-9 positivity from tears of the patients in the study (Inflammadry kit Quidel corporation). Patients were prescribed osmoprotective lubricating eye drops (Osmodrops, Cipla Ltd) four times a day and cyclosporine A 0.05% eye drops (Imudrops, Cipla Ltd) twice a day for 6 months. Efficacy of the formulations was evaluated by OSDI scores, Schirmer’s test, TBUT change, reduction in ocular surface staining, and reduction in MMP-9 levels after 6 months of usage. Check P value and add from resultsResults:After 6 months of topical therapy, improvement was observed in OSDI scores (mean pretreatment: 25.7 ± 12.8, and mean posttreatment: 15.2 ± 8.4), P < 0.001. There was also reduction number of patients who were MMP-9 positive. Out of 75 eyes that tested MMP-9 positive, 70.66% showed reduction in MMP-9 levels P < 0.0001). Ocular surface staining also improved.Conclusion:Topical osmoprotective lubricating eye drops and cyclosporine A 0.05% reduce inflammation in cases of DED, which correlates with improvement in OSDI scores, ocular surface staining, and reduction in inflammation as measured by levels of tear MMP-9.

The effect of acute exercise on environmentally induced symptoms of dry eye.

The purpose of this study was to investigate the effects of acute exercise on environmentally induced symptoms of dry eye. Twelve participants without dry eye disease volunteered to complete three experimental visits in a randomized order; (1) control condition seated for 1 h at a relative humidity (RH) of 40% (CONT), (2) dry condition seated for 1 h at a RH of 20% (DRY), and (3) exercise condition seated for 40 min followed by 20 min of cycling exercise at a RH of 20% (EXER). Tear volume, tear matrix metalloproteinase 9 (MMP‐9), perception of dry eye symptoms (frequency and severity), core temperature, and ocular surface temperature (OST) were measured at the end of each exposure. The perception of dry eye frequency and MMP‐9 concentration were significantly higher in DRY compared to CONT (P < 0.012), with no differences in EXER compared to CONT. The results suggest that an acute bout of exercise may attenuate symptoms of environmentally induced dry eye, and warrant further research.

The association between demodex infestation and ocular surface manifestations in meibomian gland dysfunction

To investigate the association between ocular demodex folliculorum infestation and ocular surface manifestations in meibomian gland dysfunction (MGD). Eight-six patients with MGD were enrolled. All enrolled subjects were tested in the following sequence: ocular surface disease index (OSDI), slit-lamp biomicroscope examination, corneal surface regularity index (SRI) and surface asymmetry index (SAI), tear fluid collection, fluorescein tear film break-up time (F-BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT) and demodex folliculorum counting. Tear matrix metalloproteinase (MMP)-9 activity was assessed using MMP-9 activity assay kit. Among 86 MGD patients, 40 were positive for demodex. The ocular demodex-positive group showed significantly increased scores of OSDI (25.96±13.74 vs 18.07±11.55, P=0.01), lid margin abnormality (2.38±0.87 vs 1.98±0.91, P=0.04) and CFS (1.28±2.00 vs 0.94±1.36, P=0.01) compared to the ocular demodex-free group. The tear MMP-9 activity was higher in the ocular demodex-positive group (102.9±32.4 ng/mL) than the ocular demodex-free group (46.2±19.2 ng/mL, P=0.03). There was no significant difference in meibum quality and expressibility, SRI, SAI, F-BUT and SIT between the two groups (P>0.05 for each). No significant correlation was noted between the number of demodex and ocular surface parameters in demodex-positive MGD group (P>0.05 for each). Ocular demodex folliculorum infestation may be associated with ocular discomfort and ocular surface damage in MGD.

Antioxidant and Osmoprotecting Activity of Taurine in Dry Eye Models.

To assess the protective effects of ophthalmic formulations based on taurine (TAU) and sodium hyaluronate (SH) in ocular surface. Rabbit corneal epithelial cells [Statens Seruminstitut Rabbit Cornea (SIRC)] were subjected to oxidative stress (1 mM H2O2) and treated with the following formulations: 0.2% SH, 0.4% SH, 0.4% SH +0.5% TAU. Reactive oxygen species (ROS) were evaluated by commercial kit. Dry eye was induced by atropine sulfate and topical treatment was carried out with the following formulations: 0.2% SH, 0.4% SH, 0.4% SH +0.5% TAU. Schirmer's test, tear breakup time (TBUT), and tear osmolarity were evaluated. Furthermore, tear matrix metalloproteinase 9 (MMP-9) expression was assessed by Western blot. TAU significantly (P < 0.05) decreased ROS production in SIRC after oxidative stress. Topical administration of atropine in the rabbit eye significantly (P < 0.05) reduced tear volume and TBUT. Tear osmolarity was also significantly (P < 0.05) modified by atropine treatment. All the altered parameters were significantly (P < 0.05) reversed by 0.5% TAU +0.4% SH treatment; furthermore, this formulation was more effective than SH alone. Moreover, tear levels of MMP-9 were significantly (P < 0.05) lower in the group treated with 0.5% TAU +0.4% SH. Altogether these data suggest that TAU has a relevant antioxidant effect in corneal epithelial cells and prevents the ocular surface damage elicited by atropine. Therefore, our findings suggest that TAU in combination with SH may be useful in clinical practice to manage ocular surface diseases.

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

To evaluate the differential expression of tear matrix metalloproteinases (MMP) 2 and 9 in of patients with various forms of glaucoma. Tear samples were collected with a Schirmer's strip from 148 eyes of 113 patients (medically naïve patients with primary open-angle [POAG] or angle closure glaucoma [PACG] and those with pseudoexfoliation syndrome [PXF] or glaucoma [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 = 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 (H2O2) stress-induced effects on in vitro activities of MMP-9 in human trabecular meshwork (HTM) cells were analyzed. The MMP-9 activity in tears was increased significantly in POAG, (n = 27), PACG (n = 24), and PXF (n = 40) eyes compared to controls (n = 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 = 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 μM H2O2-induced stress for 2 to 3 hours with approximately 80% cell death. 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.

Tear Matrix Metalloproteinases and Myeloperoxidase Levels in Patients With Boston Keratoprosthesis Type I.

To investigate the tear levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 in eyes after Boston keratoprosthesis type I (B-KPro) implantation and to correlate these markers with the established B-KPro prognostic categories. Tear washes were collected from 40 patients (7 with autoimmune disease, 2 with chemical burn, and 31 with other noncicatrizing diagnoses). Tear levels of MMPs, MPO, and tissue inhibitor of metalloproteinase-1 were quantified using multianalyte bead-based enzyme-linked immunosorbent assays. The total MMP activity was determined using a fluorimetric assay. The analytes were compared to the underlying diagnosis and other clinical factors. The MMP-8, MMP-9, and MPO levels were markedly elevated in the eyes with B-KPro (80 ± 31, 291 ± 77, and 244 ± 33 pg/μg, respectively). Chemical burn was associated with significantly higher tear MMP-8 (474 ± 376 pg/μg) and MMP-9 levels (1300 ± 635 pg/μg) compared with noncicatrizing diseases (MMP-8: 41 ± 15 pg/μg, P = 0.02 and MMP-9: 196 ± 57 pg/μg, P = 0.02) and higher MMP-9 levels compared with autoimmune diseases (MMP-8: 96 ± 65 pg/μg, P = 0.21 and MMP-9: 306 ± 196 pg/μg, P = 0.04). Similar analyte levels were observed in the B-KPro eye and the contralateral non-B-KPro eye of patients with bilateral diseases. MMP-8, MMP-9, and total MMP activities correlated strongly with each other. In the eyes with B-KPro, tear MMP-8 and MMP-9 levels seem to be related to the underlying ocular surface pathology and not significantly influenced by the presence of the prosthesis.

High Levels of 17β-Estradiol Are Associated with Increased Matrix Metalloproteinase-2 and Metalloproteinase-9 Activity in Tears of Postmenopausal Women with Dry Eye.

Purpose. To determine the serum levels of sex steroids and tear matrix metalloproteinases (MMP) 2 and 9 concentrations in postmenopausal women with dry eye. Methods. Forty-four postmenopausal women with dry eye and 22 asymptomatic controls were enrolled. Blood was drawn and analyzed for serum levels of sex steroids and lipids. Then, the following tests were performed: tear collection, Ocular Surface Disease Index (OSDI) questionnaire, fluorescein tear film break-up time (TBUT), corneal fluorescein staining, Schirmer test, and conjunctival impression cytology. The conjunctival mRNA expression and tear concentrations of MMP-2 and MMP-9 were measured. Results. Serum 17β-estradiol levels were significantly higher in the dry eye subjects than in the controls (P = 0.03), whereas there were no significant differences in levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and progesterone. Tear MMP-2 and MMP-9 concentrations (P < 0.001), as well as the MMP-9 mRNA expression in conjunctival samples (P = 0.02), were significantly higher in dry eye subjects than in controls. Serum 17β-estradiol levels were positively correlated with tear MMP-2 and MMP-9 concentrations and negatively correlated with Schirmer test values. Conclusions. High levels of 17β-estradiol are associated with increased matrix metalloproteinase-2 and metalloproteinase-9 activity in tears of postmenopausal women with dry eye.

Evaluation of point-of-care test for elevated tear matrix metalloproteinase 9 in post-LASIK dry eyes

AimTo evaluate the performance of a point-of-care test for detection of matrix metalloproteinase 9 (MMP-9) levels in post-laser-assisted in situ keratomileusis (LASIK) dry eyes.MethodsA comparative study between patients with mild...

Correlation between Tear Matrix Metalloproteinases and the Schirmer's Test

Correlation between Tear Matrix Metalloproteinases and the Schirmer's Test

Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca.

Neurturin has been identified as a neurotrophic factor for parasympathetic neurons. Neurturin-deficient (NRTN(-/-)) mice have defective parasympathetic innervation of their lacrimal glands. This study was conducted to evaluate tear function and ocular surface phenotype in NRTN(-/-) mice. Determined by tail genomic DNA PCR, 25 NRTN(-/-) mice and 17 neurturin-normal (NRTN(+/+)) mice aged 6 weeks to 4 months were evaluated. Aqueous tear production, tear fluorescein clearance and corneal sensation were serially measured. Corneal permeability to AlexaFluor dextran (AFD; Molecular Probes, Eugene, OR) was measured by a fluorometric assay at 485 nm excitation and 530 nm emission. Histology was evaluated in PAS-stained sections. Mucin and HLA class II (IA) antigen were assessed by immunofluorescent staining. Tear IL-1beta was measured by ELISA, and tear matrix metalloproteinase (MMP)-9 by zymography. Gene expression in the corneal epithelia was analyzed by semiquantitative RT-PCR. In comparison to that in age-matched NRTN(+/+) mice, aqueous tear production, tear fluorescein clearance, and corneal sensation were significantly reduced in NRTN(-/-) mice, whereas corneal permeability to AFD was significantly increased. Immunoreactive MUC-4 and -5AC mucin and goblet cell density (P < 0.001) in the conjunctiva of NRTN(-/-) mice were lower than in NRTN(+/+) mice. The expression of MUC-1 and -4 mRNA by the corneal epithelium was reduced in NRTN(-/-) mice. There were a significantly greater number of IA antigen-positive conjunctival epithelial cells in NRTN(-/-) mice than NRTN(+/+) mice. Tear fluid IL-1beta and MMP-9 concentrations and the expression of IL-1beta, TNF-alpha, macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), and MMP-9 mRNA by the corneal epithelia were significantly increased in NRTN(-/-) mice, compared with NRTN(+/+) mice. Neurturin-deficient mice show phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca. This model supports the importance of a functional ocular surface-central nervous system-lacrimal gland sensory-autonomic neural network in maintaining ocular surface health and homeostasis.