June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Matrix Metalloproteinases-8, -9 and Myeloperoxidase are Elevated in the Tears of Patients with Ocular Cicatricial Pemphigoid and Stevens-Johnson Syndrome
Author Affiliations & Notes
  • Samer Arafat
    Massachusetts Eye and Ear Infirmary, Boston, MA
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Ana Suelves
    Massachusetts Eye Research and Surgery Institution, Cambridge, MA
  • Sandra Spurr-Michaud
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, MA
  • James Chodosh
    Massachusetts Eye and Ear Infirmary, Boston, MA
  • C. Stephen Foster
    Massachusetts Eye Research and Surgery Institution, Cambridge, MA
  • Claes Dohlman
    Massachusetts Eye and Ear Infirmary, Boston, MA
  • Ilene Gipson
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Footnotes
    Commercial Relationships Samer Arafat, None; Ana Suelves, None; Sandra Spurr-Michaud, None; James Chodosh, Alcon (C), Allergan (C), 3-V Biosciences (C), Novabay (C); C. Stephen Foster, Abbott Medical Optics (C), Abbott Medical Optics (F), Alcon Laboratories, Inc. (C), Alcon Laboratories, Inc. (F), Allergan, Inc. (C), Allergan, Inc. (F), Eyegate Pharmaceuticals, Inc. (I), Eyegate Pharmaceuticals, Inc. (F), IOP Opthalmics (C), Ista Pharmaceuticals (C), Lux Biosciences, Inc. (C), Lux Biosciences, Inc. (F), Novartis Pharmaceuticals Corporation (C), Novartis Pharmaceuticals Corporation (F), XOMA Ltd (C); Claes Dohlman, None; Ilene Gipson, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 976. doi:https://doi.org/
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      Samer Arafat, Ana Suelves, Sandra Spurr-Michaud, James Chodosh, C. Stephen Foster, Claes Dohlman, Ilene Gipson; Matrix Metalloproteinases-8, -9 and Myeloperoxidase are Elevated in the Tears of Patients with Ocular Cicatricial Pemphigoid and Stevens-Johnson Syndrome. Invest. Ophthalmol. Vis. Sci. 2013;54(15):976. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To determine levels of matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and inflammatory marker myeloperoxidase (MPO) in the tears of patients with ocular cicatricial pemphigoid (OCP) and Stevens-Johnson syndrome (SJS).

Methods: Tears were collected from 7 SJS, 38 OCP and 40 post-cataract (control) eyes. 60μL of sterile balanced salt solution was instilled on each eye and tears washes were recovered with a micropipette. The tear concentrations of MMP-2, -3, -7, -8, -9 and -12 (ng/mL) in each eye were measured using a Fluorokine® Human MMP MultiAnalyte Profiling (MAP) Kit. TIMP-1 and MPO concentrations (ng/mL) were measured using a Fluorokine® human Cardiac B MAP Kit. Both assays were run on a Bio-Rad Bio-Plex analyzer powered by Luminex® technology. Total MMP activity was measured fluorometrically using an OmniMMP™ RED fluorogenic substrate. Values for all assays were standardized to the protein mass loaded in each assay.

Results: The concentrations (ng/μg total protein) of MMP-8, -9 and MPO were statistically higher in tears of patients with SJS (4.3 ± 2.0, 10.2 ± 4.5 and 6.7 ± 2.0, respectively) than in OCP (0.4 ± 0.2, 0.9 ± 0.4 and 1.5 ± 0.4, respectively), and both were significantly higher than in control (0.01 ± 0.003, 0.06 ± 0.01 and 0.4 ± 0.1, respectively). The ratio of MMP-8/TIMP-1 and MMP-9/TIMP-1 were statistically higher in SJS (7.4 ± 3.4 and 16.2 ± 6.6, respectively) than in OCP (1.1 ± 0.6 and 4.6 ± 2.5, respectively) and both were significantly higher than in control (0.01 ± 0.003 and 0.05 ± 0.01, respectively). The total MMP specific activity (RFU/min/μg protein) was higher in SJS (25.02 ± 10.60) than in both OCP (4.75 ± 2.73) and control (1.25 ± 0.87). Spearman rank correlation tests showed significant correlations between MMP-8 and MMP-9, and between MMP-9 and MPO across all groups. MMP-8 correlated with MPO in control and OCP patients (p < 0.0001), and to a lesser extent with SJS (p = 0.066).

Conclusions: Since activated neutrophils are known to be a source of MMP-8, -9 and MPO, the high levels of these enzymes in the tears of SJS and OCP patients and the strong correlation between MMP-8, MMP-9 with MPO suggest that inflammatory cells are the primary source of the elevated enzymes. In addition to MMP-8 and MMP-9, MPO was found to be a marker of inflammatory ocular surface disease.

Keywords: 479 cornea: clinical science • 486 cornea: tears/tear film/dry eye • 514 enzymes/enzyme inhibitors  
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