Mouse model of ocular hypertension with retinal ganglion cell degeneration

Ryo Mukai, Dong Ho Park, Yoko Okunuki, Eiichi Hasegawa, Garrett Klokman, Clifford B. Kim, Anitha Krishnan, Meredith Gregory-Ksander, Deeba Husain, Joan W. Miller, Kip M. Connor

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives Ocular hypertension is a primary risk factor for glaucoma and results in retinal ganglion cell (RGC) degeneration. Current animal models of glaucoma lack severe RGC cell death as seen in glaucoma, making assessment of physiological mediators of cell death difficult. We developed a modified mouse model of ocular hypertension whereby long-lasting elevation of intraocular pressure (IOP) is achieved, resulting in significant reproducible damage to RGCs. Results In this model, microbeads are mixed with hyaluronic acid and injected into the anterior chamber of C57BL/6J mice. The hyaluronic acid allows for a gradual release of microbeads, resulting in sustained blockage of Schlemm’s canal. IOP elevation was bimodal during the course of the model’s progression. The first peak occurred 1 hours after beads injection, with an IOP value of 44.69 ± 6.00 mmHg, and the second peak occurred 6–12 days post-induction, with an IOP value of 34.91 ± 5.21 mmHg. RGC damage was most severe in the peripheral retina, with a loss of 64.1% compared to that of untreated eyes, while the midperiphery exhibited a 32.4% loss, 4 weeks following disease induction. Conclusions These results suggest that sustained IOP elevation causes more RGC damage in the periphery than in the midperiphery of the retina. This model yields significant and reproducible RGC degeneration.

Original languageEnglish
Article numbere0208713
JournalPloS one
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Ocular Hypertension
Retinal Ganglion Cells
Intraocular Pressure
hypertension
eyes
animal models
glaucoma
Glaucoma
hyaluronic acid
Cell death
Hyaluronic Acid
Microspheres
retina
cells
Retina
cell death
Cell Death
Anterior Chamber
Canals
Inbred C57BL Mouse

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Mukai, R., Park, D. H., Okunuki, Y., Hasegawa, E., Klokman, G., Kim, C. B., ... Connor, K. M. (2019). Mouse model of ocular hypertension with retinal ganglion cell degeneration. PloS one, 14(1), [e0208713]. https://doi.org/10.1371/journal.pone.0208713

Mouse model of ocular hypertension with retinal ganglion cell degeneration. / Mukai, Ryo; Park, Dong Ho; Okunuki, Yoko; Hasegawa, Eiichi; Klokman, Garrett; Kim, Clifford B.; Krishnan, Anitha; Gregory-Ksander, Meredith; Husain, Deeba; Miller, Joan W.; Connor, Kip M.

In: PloS one, Vol. 14, No. 1, e0208713, 01.01.2019.

Research output: Contribution to journalArticle

Mukai, R, Park, DH, Okunuki, Y, Hasegawa, E, Klokman, G, Kim, CB, Krishnan, A, Gregory-Ksander, M, Husain, D, Miller, JW & Connor, KM 2019, 'Mouse model of ocular hypertension with retinal ganglion cell degeneration', PloS one, vol. 14, no. 1, e0208713. https://doi.org/10.1371/journal.pone.0208713
Mukai, Ryo ; Park, Dong Ho ; Okunuki, Yoko ; Hasegawa, Eiichi ; Klokman, Garrett ; Kim, Clifford B. ; Krishnan, Anitha ; Gregory-Ksander, Meredith ; Husain, Deeba ; Miller, Joan W. ; Connor, Kip M. / Mouse model of ocular hypertension with retinal ganglion cell degeneration. In: PloS one. 2019 ; Vol. 14, No. 1.
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