Mouse model of ocular hypertension with retinal ganglion cell degeneration

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 mod...

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Veröffentlicht in:PloS one 2019-01, Vol.14 (1), p.e0208713-e0208713
Hauptverfasser: 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
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container_title PloS one
container_volume 14
creator 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
description 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. 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. 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.
doi_str_mv 10.1371/journal.pone.0208713
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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. 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. 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30640920</pmid><doi>10.1371/journal.pone.0208713</doi><tpages>e0208713</tpages><orcidid>https://orcid.org/0000-0003-1796-9232</orcidid><orcidid>https://orcid.org/0000-0002-2048-9080</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acids
Angiogenesis
Animal models
Animals
Anterior chamber
Automation
Beads
Biology and Life Sciences
Blockage
Cell cycle
Cell death
Complications and side effects
Damage
Degeneration
Disease Models, Animal
Eye (anatomy)
Field study
Glaucoma
Glaucoma - metabolism
Glaucoma - physiopathology
Hyaluronic acid
Hypertension
Immunohistochemistry
Intraocular pressure
Intraocular Pressure - physiology
Laboratory animals
Laboratory rats
Male
Medical schools
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Microspheres
Nanoparticles
Ocular Hypertension - metabolism
Ocular Hypertension - physiopathology
Ophthalmology
Physical Sciences
Retina
Retina - metabolism
Retina - physiopathology
Retinal Degeneration - metabolism
Retinal Degeneration - physiopathology
Retinal ganglion cells
Retinal Ganglion Cells - metabolism
Retinal Ganglion Cells - pathology
Risk analysis
Risk factors
Tomography, Optical Coherence
title Mouse model of ocular hypertension with retinal ganglion cell degeneration
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