Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Targeted genetic defects in elastic fibers cause biomechanical weakening of mouse sclera during physiological dynamic intraocular pressure changes
Author Affiliations & Notes
  • Gianfranco Bianco
    Opthalmology and Visual Sciences, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Samuel Insignares
    Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Massimo A. Fazio
    Opthalmology and Visual Sciences, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
    Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • John Kuchtey
    Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Rachel Wang Kuchtey
    Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee, United States
    Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Gianfranco Bianco None; Samuel Insignares None; Massimo Fazio Heidelberg Engineering, Code F (Financial Support), Topcon Healthcare, Code F (Financial Support); John Kuchtey None; Rachel Kuchtey None
  • Footnotes
    Support  NIH Grant R01EY020894
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 2508. doi:
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      Gianfranco Bianco, Samuel Insignares, Massimo A. Fazio, John Kuchtey, Rachel Wang Kuchtey; Targeted genetic defects in elastic fibers cause biomechanical weakening of mouse sclera during physiological dynamic intraocular pressure changes. Invest. Ophthalmol. Vis. Sci. 2024;65(7):2508.

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

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Abstract

Purpose : Changes of scleral biomechanics play a critical role in optic nerve health. Analyzing scleral biomechanics could contribute to elucidating the etiology of glaucoma and altering their characteristics could prove to be an effective novel treatment for glaucoma patients. Here we tested the hypothesis that elastic fiber defects caused by genetic mutations result in changes in scleral biomechanics in mouse eyes.

Methods : We measured the dynamic scleral biomechanical response of intact 16-week-old mouse eyes comparing two experimental groups: wild type (wt, n=5) and a newly created double mutant line (dbm, Fbn1C1041G/+;Lxol1-/-, n=7) with elastic fiber defects. Posterior sclera response was measured during cyclic intraocular pressure (IOP) variations within a physiological range at different IOP amplitudes (Δ= 5, 10, 15 mmHg) and different frequencies (f= 0.5, 1, 2 Hz). Scleral strain was measured around the optic nerve head region by a custom three-dimensional (3D) optical method (3D-Digital Image Correlation) to provide high dynamic acquisition rates (85 Hz). Cyclic IOP variations were induced and controlled by an ocular infusion device designed for high-accuracy dynamic mechanical analysis (Electroforce 5500) and measured by a high sampling rate piezoelectric sensor (Millar Mikro-Tip).

Results : Biomechanical weakening was defined by the largest peak strain measured during 6-cycle IOP variations. Statistical comparison by unpaired t-test (Fig.1,2) revealed a significant biomechanical weakening (p<0.05) of the posterior sclera of dbm mice group during dynamic IOP changes in all loading conditions compared to wt mice.

Conclusions : Targeted genetic defects in elastic fibers cause biomechanical weakening of posterior sclera in mice during physiological dynamic IOP variations. Such investigation could provide mechanistic insight into the role of biomechanics of the ONH in glaucoma.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

 

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