September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Assessment of age-related eye morphology and aqueous humor flow dynamics in the DBA/2J mouse model of pigmentary glaucoma using ocular MRI and anterior chamber iPerfusion systems.
Author Affiliations & Notes
  • Darragh Crosbie
    Genetics Department, Trinity College Dublin, Dublin, Ireland
  • James Keaney
    Genetics Department, Trinity College Dublin, Dublin, Ireland
    Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis
  • Joseph M. Sherwood
    Imperial College London, London, United Kingdom
  • Darryl R. Overby
    Imperial College London, London, United Kingdom
  • W Daniel Stamer
    Duke University, Durham, North Carolina, United States
  • Lawrence Tam
    Genetics Department, Trinity College Dublin, Dublin, Ireland
  • Peter Humphries
    Genetics Department, Trinity College Dublin, Dublin, Ireland
  • Footnotes
    Commercial Relationships   Darragh Crosbie, None; James Keaney, None; Joseph Sherwood, None; Darryl Overby, None; W Stamer, None; Lawrence Tam, None; Peter Humphries, None
  • Footnotes
    Support  NONE
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5145. doi:
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      Darragh Crosbie, James Keaney, Joseph M. Sherwood, Darryl R. Overby, W Daniel Stamer, Lawrence Tam, Peter Humphries; Assessment of age-related eye morphology and aqueous humor flow dynamics in the DBA/2J mouse model of pigmentary glaucoma using ocular MRI and anterior chamber iPerfusion systems.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5145.

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

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Abstract

Purpose : Using contrast enhanced Gadolinium(Gd)-MRI and a novel anterior chamber perfusion system (iPerfusion) age related changes in the morphology and flow dynamics of aqueous humor (AqH) were compared between wild-type C57BL/6 and glaucomatous DBA/2J mouse eyes.

Methods : WT and DBA mouse eyes were compared at 3 and 9 months using a rodent-specific 7T MRI. Pre-scan images without contrast agent were used to assess eye anatomy: anterior chamber (AC) and vitreous body (VB) morphology, and eye and lens size. Gd-DTPA (Magnevist) was injected intravenously at time 0 and the eyes were scanned each minute for the subsequent hour to measure AqH flow. In order to reliably assess differences in AqH outflow, a novel AC perfusion system (iPerfusion) was used to measure outflow facility.

Results : We treated WT mice with topical latanoprost eyedrops to demonstrate the ability of MRI to assess AqH flow dynamics in the AC. Latanoprost-treated eyes showed a decreased rate of Gd accumulation (Diff = -1.274 ± 0.3973(%/min), p = 0.0184) and peak Gd intensity in the AC in comparison to saline treated contralateral eyes. Furthermore, MRI images showed an age-related increase in AC area, AC depth and eye size in DBA mice as compared to WT mice from 3 to 9 mo (p<0.0001, N = 6). In addition, no significant changes were observed in either rate of AC Gd accumulation or Gd peak intensity in the AC of WT mice, and no difference was found between 3-mo wt and DBA mice. However, 9-mo DBA animals showed a decrease in Gd accumulation (Diff 10.33 ± 2.779, p<0.01) and peak Gd intensity. Facility in DBA2J shows an average of 46% reduction from 9 to 6 mo (N=4). Similarly, leakage of gadolinium from the ciliary body posteriorly into the VB was observed in 9-mo DBA mice and not in WT mice.

Conclusions : MRI is a useful tool for in vivo analysis of the eye, as demonstrated for a common mouse model of glaucoma. It allows for morphological measurements of mouse eye structures and can be used to assess AqH dynamics. The DBA model shows age related changes in AC morphology and outflow facility that is not seen in WT mice; although more animals need to be tested to determine whether facility is significantly different. Gd-MRI analysis with iPerfusion data indicates that aged DBA mice also have a lower and dysregulated AqH inflow in comparison to aged WT mice.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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