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Exp Eye Res. 2019 Jun 15;185:107703. doi: 10.1016/j.exer.2019.107703. [Epub ahead of print]

Effect of ocular hypertension on the pattern of retinal ganglion cell subtype loss in a mouse model of early-onset glaucoma.

Author information

1
North Texas Eye Research Institute, Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, United States.
2
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States.
3
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, United States; (d)VA Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care System, Iowa City, IA, United States.
4
Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, United States. Electronic address: cmmcdowell@wisc.edu.

Abstract

Glaucoma is a neurodegenerative disease with elevated intraocular pressure as one of the major risk factors. Glaucoma leads to irreversible loss of vision and its progression involves optic nerve head cupping, axonal degeneration, retinal ganglion cell (RGC) loss, and visual field defects. Despite its high global prevalence, glaucoma still remains a major neurodegenerative disease. Introduction of mouse models of experimental glaucoma has become integral to glaucoma research due to well-studied genetics as well as ease of manipulations. Many established inherent and inducible mouse models of glaucoma are used to study the molecular and physiological progression of the disease. One such model of spontaneous mutation is the nee model, which is caused by mutation of the Sh3pxd2b gene. In both humans and mice, mutations disrupting function of the SH3PXD2B adaptor protein cause a developmental syndrome including secondary congenital glaucoma. The purpose of this study was to characterize the early onset nee glaucoma phenotype on the C57BL/6J background and to evaluate the pattern of RGC loss and axonal degeneration in specific RGC subtypes. We found that the B6.Sh3pxd2bnee mutant animals exhibit glaucoma phenotypes of elevated intraocular pressure, RGC loss and axonal degeneration. Moreover, the non-image forming RGCs survived longer than the On-Off direction selective RGCs (DSGC), and the axonal death in these RGCs was independent of their respective RGC subtype. In conclusion, through this study we characterized an experimental model of early onset glaucoma on a C57BL/6J background exhibiting key glaucoma phenotypes. In addition, we describe that RGC death has subtype-specific sensitivities and follows a specific pattern of cell death under glaucomatous conditions.

KEYWORDS:

Glaucoma; Intraocular pressure; Optic nerve; RGC subtype

PMID:
31211954
DOI:
10.1016/j.exer.2019.107703

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