Matrix Metalloproteinase 9 and Transglutaminase 2 Expression at the Ocular Surface in Patients with Different Forms of Dry Eye Disease

Aragona, Pasquale; Aguennouz, M.; Rania, Laura; Postorino, Elisa Imelde; Sommario, Margherita Serena; Roszkowska, Anna M.; Pasquale, M. G. De; Pisani, Antonina; Puzzolo, Domenico

doi:10.1016/j.ophtha.2014.07.048

Cited by 123 publications

(109 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MMP-9 gene expression and immunoreactivity were also found elevated in conjunctival epithelial cells obtained from normal subjects and patients with SS-associated dry eye and meibomian gland disease (MGD) that also causes tear instability. 72 Levels of MMP-9 transcripts were significantly higher in both types of tear dysfunction than asymptomatic controls, and MMP-9 expression was higher in SS than MGD. MMP-9 expression significantly correlated with clinical severity in the SS group.…”

mentioning

confidence: 82%

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

View full text Add to dashboard Cite

Dry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. Increased levels and activities of matrix metalloproteinases (MMPs), particularly MMP-9, have been detected in the tears and ocular surface epithelial and inflammatory cells in dry eye. MMPs have been found to participate in disruption of tight junctions in the apical cornea epithelium leading to their accelerated desquamation and barrier disruption. This review summarizes evidence showing the contribution of MMPs to dry eye pathogenesis and their roles as biomarkers and therapeutic targets. Keywords: matrix metalloproteinase, dry eye, keratitis sicca, cornea, barrier function, Sjögren syndrome Dry eye overviewDry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. It affects millions of people worldwide and is one of the most frequent conditions for which patients seek eye care.1 Aging and female sex are significant risk factors for dry eye which increases in prevalence around the fifth decade, with further increase every decade thereafter.2-13 Prevalence of dry eye varies from 2% to 50%, depending on the population studied and the diagnostic criteria for dry eye (symptom questionnaire vs. objective signs). [1][2][3]6,7,[9][10][11][14][15][16][17][18][19][20][21][22][23] There is scarce information about the natural history of dry eye, but there is a recognized disconnection between signs and symptoms; patients tend to be more symptomatic at early stages.24,25 Dry eye causes corneal irregularity [26][27][28] and decreases functional vision by altering contrast sensitivity [29][30][31] and, therefore, decreases quality of life with a significant burden on the individual as well as the society. 23,[32][33][34][35] A meta-analysis of 22 published studies showed increased odds ratio for depression and anxiety in patients with ocular Sjögren syndrome (SS). 36 There is increased evidence that dry eye is an inflammatory disease, and this review will focus on matrix metalloproteinases (MMPs) and their role in the pathogenesis of dry eye. Cornea barrier disruption is a feature of dry eyeAs the principal lens of the eye, the cornea has unique features to maintain its transparency and smooth surface that include a lack of blood vessels and a multilayered stratified, non-cornifying epithelium. The differentiated apical epithelial cells produce

show abstract

mentioning

confidence: 82%

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

View full text Add to dashboard Cite

show abstract

“…17 MMP-9 is also understood to play a pathological role in inflammatory disease, responsible for disrupting epithelial layers by cleaving tight junction proteins occludin and zonula occludens-1. 18 Tear fluid hyperosmolarity, which is seen in some patients with DE, has been shown to trigger the release of MMP-9, thus initiating a cycle of progressive inflammation. 18–22 The mitogen-activated protein kinase ( MAPK ) cascade is stimulated by corneal epithelial surface hyperosmolarity and inflammatory factors interleukin ( IL )-1B and tumor necrosis factor ( TNF )-α.…”

Section: Introductionmentioning

confidence: 99%

Dry Eye Profiles in Patients with a Positive Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test Versus Negative Patients

et al. 2016

View full text Add to dashboard Cite

Purpose To compare dry eye (DE) symptoms and signs in subjects who tested positive versus those who tested negative for ocular surface matrix metalloproteinase 9 (MMP-9) using the InflammaDry point of care test (RPS, Sarasota, FL). Methods In this cross-sectional study, individuals seen in the Miami Veterans Affairs eye clinic with DE symptoms, as evidenced by DE questionnaire 5 (DEQ5) ≥6, were given standardized questionnaires to assess DE symptoms and ocular and non-ocular pain complaints. Also, a complete evaluation was conducted to measure ocular surface signs of DE. MMP-9 testing was performed using the InflammaDry once in each eye, per the manufacturer’s instructions. The main outcome measure was a comparison of DE symptoms and signs in MMP-9 positive versus negative subjects. Results Of 128 subjects, 50 (39%) were positive for MMP-9 for InflammaDry testing in either eye. No statistically significant differences in mental health indices, DE symptoms, or ocular surface signs were seen in subjects based on MMP-9 status. Conclusion In our population, there was no difference in the DE profile by both symptoms and signs between those testing positive versus negative for MMP-9 on the ocular surface. This suggests that clinical exam alone cannot predict patients with clinically significant inflammation.

show abstract

“…A score ‡3 was considered abnormal. 25,26 The corneal sensitivity measurements were performed using the Cochet-Bonnet esthesiometer (Luneau Ophtalmologie, Chartres, France) as previously described. 27 The IOP was measured using a Goldmann applanation tonometer after topical anesthesia with unpreserved 0.4% oxybuprocaine hydrochloride (Novesina; Novartis Farma, Origgio VA, Italy).…”

Section: Ophthalmologic Assessmentmentioning

confidence: 99%

Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies

Aragona

Allegra

Postorino

et al. 2016

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

METHODS. Three groups of subjects were considered: group 1, twenty normal subjects; group 2, fifteen patients with monoclonal gammopathy of undetermined significance (MGUS); group 3, eight patients with smoldering multiple myeloma and eight patients with untreated multiple myeloma. After hematologic diagnosis, patients underwent ophthalmologic exam and in vivo confocal microscopic study. The statistical analysis was performed using ANOVA and Student-Newman-Keuls tests and receiver operating characteristic (ROC) curve analysis.RESULTS. Epithelial cells of gammopathic patients showed significantly higher reflectivity than controls, demonstrated by optical density (P < 0.001). Subbasal nerve density, branching, and beading were significantly altered in gammopathic patients (P ¼ 0.01, P ¼ 0.02, P ¼ 0.02, respectively). The number of keratocytes was significantly reduced in neoplastic patients (P < 0.001 versus both normal and MGUS) in the anterior, medium, and posterior stroma. The ROC curve analysis showed good sensitivity and specificity for this parameter. Group 2 and 3 keratocytes showed higher nuclear and cytoplasmatic reflectivity in the medium and posterior stroma. Endothelial cells were not affected. CONCLUSIONS.Patients with neoplastic gammopathies showed peculiar alterations of the keratocyte number, which appeared significantly reduced. A follow-up with corneal confocal microscopy of patients with MGUS is suggested as a useful tool to identify peripheral tissue alterations linked to possible neoplastic disease development.

show abstract

Matrix Metalloproteinase 9 and Transglutaminase 2 Expression at the Ocular Surface in Patients with Different Forms of Dry Eye Disease

Cited by 123 publications

References 48 publications

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Dry Eye Profiles in Patients with a Positive Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test Versus Negative Patients

Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies

Contact Info

Product

Resources

About