Membrane Array Analysis of Tear Proteins in Ocular Cicatricial Pemphigoid

Chan, Matilda F.; Sack, Robert A.; Quigley, David A.; Sathe, Sonal; Vijmasi, Trinka; Li, Shimin; Holsclaw, Douglas S.; Strauss, Erich C.; McNamara, Nancy

doi:10.1097/opx.0b013e31821ddc6c

Cited by 24 publications

(18 citation statements)

References 7 publications

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“…Membrane array analysis of OCP tears in active disease revealed markedly elevated MMP-9 thought to be released by activated neutrophils 26 . MPO is a well-established marker of neutrophil infiltration whose activity has been used to quantitate the density of polymorphonuclear cells in corneal and conjunctival tissues 27,28 .…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Interblinking microtrauma owing to eyelid margin or cicatrical conjunctival changes are associated with persistent ocular surface inflammation in Stevens-Johnson syndrome and ocular cicatrical pemphigoid. 34,35 Most ocular GVHD patients have concurrent GVHD in other organs and are primarily managed by a general physician. This may delay the diagnosis of ocular GVHD, especially in the early stage, and result in irreversible damage to the ocular surfaces.…”

Section: Tear Osmolarity Has Been Proposed As the ''Goldmentioning

confidence: 99%

Tear Osmolarity and Ocular Surface Parameters as Diagnostic Markers of Ocular Graft-Versus-Host Disease

Yoo

Hwang

et al. 2015

American Journal of Ophthalmology

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“…As for flare in the anterior chamber, we measured aqueous protein levels directly, because it was often difficult to assess the flare accurately using slit-lamp microscopy in the eyes with corneal opacity. We excluded 18 eyes with ocular comorbidities (8 eyes with a history of exfoliation syndrome, 3 eyes with chemical burn, 2 eyes with ocular cicatricial pemphigoid, 1 eye with aniridia, 1 eye with endotheliitis, 1 eye with Stevens-Johnson syndrome, 1 with exposure keratitis, and 1 eye with iritis), because previous studies showed that aqueous cytokine levels are elevated in eyes with exfoliation syndrome due to breakdown of the blood-aqueous barrier (BAB), 19 and that tear cytokine levels are elevated in inflammatory ocular surface diseases, 20,21 which can affect aqueous cytokine levels due to breakdown of the corneal epithelial barrier. 22 In the eyes with cataract and bullous keratopathy, when we perform two-step surgery, we always perform cataract surgery first, followed by DSAEK, with an interval of more than 3 months.…”

Section: Patientsmentioning

confidence: 99%

Iris Damage Is Associated With Elevated Cytokine Levels in Aqueous Humor

Aketa

Yamaguchi

Suzuki

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To evaluate the association between iris damage and cytokine levels in the aqueous humor (AqH). METHODS.A total of 201 AqH samples from 201 consecutive patients (mean age 73.7 6 10.6) were collected at the beginning of corneal transplantation or cataract surgery. Iris damage of each case was assessed from preoperative slit-lamp findings based on its severity. The subjects were classified into three groups: eyes without iris damage (126 eyes), eyes with mild iris damage (51 eyes), and eyes with severe iris damage (24 eyes RESULTS. The levels of aqueous protein, IL-1a, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-17A, MCP-1, TNF-a, E-selectin, P-selectin, and sICAM-1 in eyes with mild and severe iris damage were higher than in those without iris damage (P < 0.033). Multivariate analyses of clinical factors revealed that iris damage was associated with the history of complicated glaucoma, and the number of previous intraocular surgeries. The levels of AqH IL-6, IL-8, IL-13, MIP1a, TNF-a, and sICAM-1 were significantly elevated in eyes with mild and severe iris damage in phakic eyes, and the levels of AqH IL-8 and sICAM-1 were significantly elevated in eyes with severe iris damage in pseudophakic eyes, compared with the eyes without iris damage (P < 0.045). CONCLUSIONS.Iris damage was associated with the elevation in the levels of aqueous protein and cytokines.

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Membrane Array Analysis of Tear Proteins in Ocular Cicatricial Pemphigoid

Cited by 24 publications

References 7 publications

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

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

Tear Osmolarity and Ocular Surface Parameters as Diagnostic Markers of Ocular Graft-Versus-Host Disease

Iris Damage Is Associated With Elevated Cytokine Levels in Aqueous Humor

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