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Evaluation of matrix metalloproteinases and tissue inhibitors of metalloproteinases in aqueous humor of dogs with versus without naturally occurring primary angle-closure glaucoma

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  • 1 Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA
  • | 2 Department of Population and Quantitative Health Sciences, UMass Chan Medical School, University of Massachusetts, Worcester, MA

Abstract

OBJECTIVE

To compare concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aqueous humor from ophthalmologically normal dogs and dogs with naturally occurring primary angle-closure glaucoma (cPACG).

SAMPLE

Aqueous humor samples from 12 eyes with cPACG and 18 ophthalmologically normal eyes of dogs.

PROCEDURES

A multiplex fluorescence-based ELISA was used to measure concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, TIMP-2, and TIMP-4. Results for eyes with versus without cPACG were compared.

RESULTS

Significantly higher mean concentrations of MMP-1 (45% higher), MMP-2 (55% higher), MMP-3 (39% higher), MMP-8 (79% higher), MMP-9 (29% higher), MMP-10 (60% higher), TIMP-1 (63% higher), and TIMP-2 (136% higher) were detected in aqueous humor from eyes with cPACG, compared with ophthalmologically normal eyes.

CLINICAL RELEVANCE

MMPs and TIMPs have pivotal roles in extracellular matrix turnover and homeostasis in the outflow pathways of the eye. Results of the present study documented higher concentrations of MMPs and TIMPs in aqueous humor samples from dog eyes with late-stage cPACG. Although, to our knowledge, TIMPs have not previously been evaluated in the context of cPACG, the markedly higher concentration of TIMPs in eyes with cPACG suggested that inhibition of proteolysis and extracellular matrix turnover might be a factor in the development of glaucoma in susceptible individuals. However, because the present study used samples from dogs with late-stage cPACG, further work is required to characterize the temporal relationship between MMP and TIMP concentration changes and onset or progression of disease.

Abstract

OBJECTIVE

To compare concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aqueous humor from ophthalmologically normal dogs and dogs with naturally occurring primary angle-closure glaucoma (cPACG).

SAMPLE

Aqueous humor samples from 12 eyes with cPACG and 18 ophthalmologically normal eyes of dogs.

PROCEDURES

A multiplex fluorescence-based ELISA was used to measure concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, TIMP-2, and TIMP-4. Results for eyes with versus without cPACG were compared.

RESULTS

Significantly higher mean concentrations of MMP-1 (45% higher), MMP-2 (55% higher), MMP-3 (39% higher), MMP-8 (79% higher), MMP-9 (29% higher), MMP-10 (60% higher), TIMP-1 (63% higher), and TIMP-2 (136% higher) were detected in aqueous humor from eyes with cPACG, compared with ophthalmologically normal eyes.

CLINICAL RELEVANCE

MMPs and TIMPs have pivotal roles in extracellular matrix turnover and homeostasis in the outflow pathways of the eye. Results of the present study documented higher concentrations of MMPs and TIMPs in aqueous humor samples from dog eyes with late-stage cPACG. Although, to our knowledge, TIMPs have not previously been evaluated in the context of cPACG, the markedly higher concentration of TIMPs in eyes with cPACG suggested that inhibition of proteolysis and extracellular matrix turnover might be a factor in the development of glaucoma in susceptible individuals. However, because the present study used samples from dogs with late-stage cPACG, further work is required to characterize the temporal relationship between MMP and TIMP concentration changes and onset or progression of disease.

Supplementary Materials

    • Supplementary Appendix (PDF 111 KB)

Contributor Notes

Corresponding author: Dr. Pumphrey (stephanie.pumphrey@tufts.edu)