TY - JOUR
T1 - Mouse model of ocular hypertension with retinal ganglion cell degeneration
AU - Mukai, Ryo
AU - Park, Dong Ho
AU - Okunuki, Yoko
AU - Hasegawa, Eiichi
AU - Klokman, Garrett
AU - Kim, Clifford B.
AU - Krishnan, Anitha
AU - Gregory-Ksander, Meredith
AU - Husain, Deeba
AU - Miller, Joan W.
AU - Connor, Kip M.
N1 - Publisher Copyright:
© 2019 Mukai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85059895155&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0208713
DO - 10.1371/journal.pone.0208713
M3 - Article
C2 - 30640920
AN - SCOPUS:85059895155
SN - 1932-6203
VL - 14
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e0208713
ER -