A mouse model of elevated intraocular pressure: Retina and optic nerve findings

Ronald L. Gross, Jianzhong Ji, Peter Chang, Mark E. Pennesi, Zhuo Yang, Jian Zhang, Samuel M. Wu, Paul R. Lichter, George L. Spaeth, John C. Heckenlively, E. Michael Van Buskirk, David L. Knox

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Abstract

Purpose: To develop and characterize a mouse model of elevated intraocular pressure (IOP) as a means to investigate the underlying cellular and genetic mechanisms of glaucomatous optic neuropathy. Methods: An experimental increase in IOP was induced in one eye of each adult C57BL/6J mouse by argon laser photocoagulation of the episcleral and limbal veins. The IOP of both eyes of each mouse was measured using an indentation tonometer prior to treatment and once a week thereafter. The mouse retinal ganglion cells (RGCs) were identified immunocytochemically using an antiserum against Thy1,2, CD90.2, and the number of RGCs was measured with confocal microscopy. The reduction in the number of RGCs was compared in the experimental and control eyes. The mechanism of RGC death after IOP elevation was investigated using TdT-mediated dUTP nick end labeling (TUNEL) staining. The pathologic changes of optic nerve following elevated IOP were characterized by light and electron microscopy. Results: After laser treatment, mean IOP was increased in the treated eyes from the control mean of 13 ± 1.8 mm Hg to 20.0 ± 2.8 mm Hg at 4 weeks. Peak IOP was 32 ± 2.5 mm Hg in the experimental group. RGC loss was 16. 9% ± 7.8% at 2 weeks (n = 6, P<.05) and 22.4% ± 7.5% at 4 weeks (n = 6, P<.05) after laser photocoagulation. TUNEL staining showed that there were marked increases in the number of apoptotic nuclei in the ganglion cell layer in the treated eyes; moreover, these TUNEL-positive cells were mostly distributed in the peripheral areas of the retina. The optic nerve axons from the eyes with elevated IOP were observed to demonstrate greater degeneration compared with the control group. Conclusions: The magnitude and duration of the elevation of the IOP supports the use of this model as a surrogate for glaucomatous optic neuropathy. The presumed apoptotic mechanism of RGC death is consistent with this assumption. Laser-induced increased IOP appears to be a viable means for future investigations of the genetic mechanisms of glaucoma.

Original languageEnglish (US)
Pages (from-to)163-171
Number of pages9
JournalTransactions of the American Ophthalmological Society
Volume101
StatePublished - Dec 1 2003

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ASJC Scopus subject areas

  • Ophthalmology

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Gross, R. L., Ji, J., Chang, P., Pennesi, M. E., Yang, Z., Zhang, J., Wu, S. M., Lichter, P. R., Spaeth, G. L., Heckenlively, J. C., Van Buskirk, E. M., & Knox, D. L. (2003). A mouse model of elevated intraocular pressure: Retina and optic nerve findings. Transactions of the American Ophthalmological Society, 101, 163-171.