June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
BXD MURINE RECOMBINANT MODELS OF GLAUCOMA SUBTYPES
Author Affiliations & Notes
  • Sophie Pilkinton
    Ophthalmology, The University of Tennessee Health Science Center Department of Ophthalmology Hamilton Eye Institute, Memphis, Tennessee, United States
  • Yooyoung Kim
    Ophthalmology, The University of Tennessee Health Science Center Department of Ophthalmology Hamilton Eye Institute, Memphis, Tennessee, United States
  • Xiangdi Wang
    Ophthalmology, The University of Tennessee Health Science Center Department of Ophthalmology Hamilton Eye Institute, Memphis, Tennessee, United States
  • TJ Hollingsworth
    Ophthalmology, The University of Tennessee Health Science Center Department of Ophthalmology Hamilton Eye Institute, Memphis, Tennessee, United States
  • Monica M Jablonski
    Ophthalmology, The University of Tennessee Health Science Center Department of Ophthalmology Hamilton Eye Institute, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Sophie Pilkinton None; Yooyoung Kim None; Xiangdi Wang None; TJ Hollingsworth None; Monica Jablonski OculoTherapy LLC, Code O (Owner)
  • Footnotes
    Support  NEI EY021200, BRIGHTFOCUS FOUNDATION, RPB CHALLENGE AWARD
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4712. doi:
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      Sophie Pilkinton, Yooyoung Kim, Xiangdi Wang, TJ Hollingsworth, Monica M Jablonski; BXD MURINE RECOMBINANT MODELS OF GLAUCOMA SUBTYPES. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4712.

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

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Abstract

Purpose : Glaucoma is a grave optic neuropathy, ultimately defined by visual field loss secondary to damage of the retinal ganglion cell (RGC) layer of the optic nerve (ON). This damage is chiefly incited by increased intraocular pressure (IOP); however, many strive to further comprehend this devastating process and formulate innovative therapeutic solutions. Our study structurally and functionally examines three polygenic, genetically distinct strains of mice from the BXD family (BXD50, BXD51, and BXD87) which develop glaucoma spontaneously in 3 forms - primary open-angle (POAG), primary angle closure (PACG), and normal tension glaucoma (NTG). This process of bidirectional translation seeks to advance understanding first in mice, then in humans alike.

Methods : Based on data on density of dead axons, grading of ON degeneration, and IOP, strains were selected to undergo further analyses. Functional included: optokinetic nystagmus (OKN), visual acuity and contrast sensitivity measurements, IOP measurements, pattern electroretinograms (PERG), and optical coherence tomography (OCT), all performed every 3 months from 1-12 months (m) of age. Structural included: paraphenylenediamine stained ON sections, immunohistochemistry, and histology at 12m.

Results : BXD50 and BXD51 demonstrate elevated IOP with age. BXD87 IOP is consistently on the high end of normal range. All strains show decreased visual acuity (VA) and contrast sensitivity (CS): BXD50 12m, BXD51 12m, BXD87 VA 12m and CS 9m. All exhibit a decrease in PERG at 12m. Assessing the iridocorneal angle with OCT, BXD50 and BXD87 mice have open angles throughout. BXD51 mice have closed angles 21/22 mice at 12m. B6 control mice show normal expression of dendritic markers while BXD50, BXD51 mice show decreased expression, confirming glaucomatous damage.

Conclusions : Reviewing the trends observed, BXD50 models POAG, BXD51 prototypes PACG, and BXD87 exhibits NTG. In conclusion, these models allow the study of spontaneous development of glaucoma via 3 distinct mechanisms. This provides an opportunity to compare pathophysiology for further characterization, creating a profound tool to explore therapeutic mechanisms and evaluate treatment efficacy.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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