July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Fluorophotometric determination of aqueous humor flow rates (AHFRs) in a canine model of ADAMTS10-Weill Marchesani syndrome-associated open-angle glaucoma (WMS-OAG)
Author Affiliations & Notes
  • Christine Harman
    Small Animal Clinical Sciences, Michigan State University , East Lansing, Michigan, United States
  • Kristin L Koehl
    Small Animal Clinical Sciences, Michigan State University , East Lansing, Michigan, United States
  • Carol B Toris
    Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, Ohio, United States
  • Leandro B C Teixeira
    Pathobiological Sciences, University of Wisconsin, Madison, Wisconsin, United States
  • Andras M Komaromy
    Small Animal Clinical Sciences, Michigan State University , East Lansing, Michigan, United States
  • Footnotes
    Commercial Relationships   Christine Harman, None; Kristin Koehl, None; Carol Toris, None; Leandro Teixeira, None; Andras Komaromy, None
  • Footnotes
    Support  NIH Grants R01-EY025752, Edward Sheppard and family
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5121. doi:
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      Christine Harman, Kristin L Koehl, Carol B Toris, Leandro B C Teixeira, Andras M Komaromy; Fluorophotometric determination of aqueous humor flow rates (AHFRs) in a canine model of ADAMTS10-Weill Marchesani syndrome-associated open-angle glaucoma (WMS-OAG). Invest. Ophthalmol. Vis. Sci. 2019;60(9):5121.

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

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Abstract

Purpose : To determine AHFRs by fluorophotometry in dogs with early and moderate stages of WMS-OAG due to a G661R missense mutation in ADAMTS10.

Methods : Nine eyes of 6 ADAMTS10-mutant dogs between 2.1-3.3 years of age were measured; 5 of these eyes were measured twice within 3-5 months. Mean intraocular pressures (IOP) ± STD were 25.4 ± 6.5 mmHg. In addition to comparison with published normative canine data, two 1-year old normal dogs were examined (IOP: 17.0 ± 3.6 mmHg). Four hours before beginning the flow measurements, 20 μL of 10% fluorescein was administered onto the corneal surface. Dogs were lightly sedated with single doses of intravenous butorphanol and midazolam to keep them calm. Fluorescein concentrations in the cornea and anterior chamber were measured 4 times at 45-minute intervals with a scanning ocular fluorophotometer (Fluorotron, OcuMetrics). Corneal thickness (pachymetry), anterior chamber depth (ultrasonography), and cornea diameter (calipers) were measured to calculate corneal and anterior chamber volumes, and subsequently AHFR using the Yablonski method. Flow rates of mutant and normal controls were compared by nonparametric Wilcoxon signed-rank test. Archival ADAMTS10-mutant ocular tissues were examined by routine histopathology to identify any morphological abnormalities of the ciliary body.

Results : AHFRs in ADAMTS10-mutant eyes were 0.2-5.8 μL (median: 2.2 μL/min). These were significantly (p<0.001) lower than our values obtained from normal control eyes (6.2-13.5 μL/min, median: 8.6 μL/min), and lower than previously published normative canine flow rates (5.5-6.8 μL/min). AHFRs did not appear to vary with stage of disease since there was no significant correlation between flow rates and IOPs. Light-microscopic examination found lens zonular dysplasia with thick mats of irregular basement membranes carpeting the surface of the ciliary epithelium in the ADAMTS10-mutant eyes.

Conclusions : AHFRs are significantly reduced in ADAMTS10-mutant dogs regardless of WMS-OAG diseases stage. A recent report (Mularczyk et al. 2018) found smaller size and fewer ciliary processes in ADAMTS10S236X/S236X WMS mice compared to controls; but similar abnormalities were not found in our ADAMTS10-mutant dogs. Other explanations for the low flow rate will have to be further investigated.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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