Relative ability of aqueous humor from dogs with and without primary angle-closure glaucoma and ADAMTS10 open-angle glaucoma to catalyze or inhibit collagenolysis

Vet Ophthalmol. 2024 May;27(3):238-247. doi: 10.1111/vop.13143. Epub 2023 Sep 1.

Abstract

Objective: The objective of the study was to compare the ability of aqueous humor (AH) from dogs with primary angle-closure glaucoma (CPACG), companion dogs without overt evidence of CPACG, and Beagles with and without ADAMTS10 open-angle glaucoma (ADAMTS10-OAG) to catalyze or inhibit collagenolysis.

Animals studied: Seventeen normal pet dogs, 27 dogs with CPACG, 19 Beagles with ADAMTS10-OAG, and 4 unaffected Beagles.

Procedures: A fluorescein-based substrate degradation assay was used to assess AH proteolytic capacity. Samples were then assayed using the same substrate degradation assay, with recombinant activated matrix metalloproteinase-2 (MMP-2) added to measure protease inhibition effects.

Results: For the protease activity assay, relative fluorescence (RF) for AH from normal pet dogs was 13.28 ± 2.25% of control collagenase while RF for AH from dogs with CPACG was 17.47 ± 4.67%; RF was 8.57 ± 1.72% for ADAMTS10-OAG Beagles and 7.99 ± 1.15% for unaffected Beagles. For the MMP-2 inhibition assay, RF for AH from normal dogs was 34.96 ± 15.04% compared to MMP-2 controls, while RF from dogs with CPACG was 16.69 ± 7.95%; RF was 85.85 ± 13.23% for Beagles with ADAMTS10-OAG and 94.51 ± 8.36% for unaffected Beagles. Significant differences were found between dogs with CPACG and both normal pet dogs and dogs with ADAMTS10-OAG and between normal pet dogs and both groups of Beagles.

Conclusions: AH from dogs with CPACG is significantly more able to catalyze proteolysis and inhibit MMP-2 than AH from normal dogs or dogs with ADAMTS10-OAG. Results suggest that pathogenesis may differ between CPACG and ADAMTS10-OAG.

Keywords: canine; extracellular matrix; glaucoma; matrix metalloproteinases (MMP); tissue inhibitors of metalloproteinases (TIMP).

MeSH terms

  • ADAMTS Proteins / genetics
  • ADAMTS Proteins / metabolism
  • Animals
  • Aqueous Humor* / chemistry
  • Aqueous Humor* / metabolism
  • Collagen / metabolism
  • Dog Diseases*
  • Dogs
  • Female
  • Glaucoma, Angle-Closure* / veterinary
  • Glaucoma, Open-Angle / metabolism
  • Glaucoma, Open-Angle / veterinary
  • Male
  • Matrix Metalloproteinase 2 / metabolism

Substances

  • Collagen
  • ADAMTS Proteins
  • Matrix Metalloproteinase 2