A mouse model of chronic ocular hypertension induced by circumlimbal suture

TitleA mouse model of chronic ocular hypertension induced by circumlimbal suture
Publication TypeJournal Article
Year of Publication2017
AuthorsLiu, H. - H., and J. Flanagan
JournalInvestigative Ophthalmology and Visual Science
Volume58
Pagination353-361
Keywordsadverse effects, animal, animal cell, animal model, animal tissue, Animals, Article, B scan, C57BL mouse, cell counting, cell function, chronic disease, circumlimbal suture technique, controlled study, cornea limbus, disease course, disease model, Disease Models, Disease Progression, electroretinogram, electroretinography, follow up, Follow-Up Studies, Ganglion cell, Glaucoma, histology, Inbred C57BL, intraocular hypertension, intraocular pressure, Limbus Corneae, male, Mice, mouse, nerve fiber degeneration, nonhuman, Ocular Hypertension, ophthalmic suture, Optical Coherence, Optical coherence tomography, pathology, pathophysiology, physiology, priority journal, retina, retinal thickness, surgery, suture, suture technique, Sutures, Tomography
Abstract

PURPOSE. To develop a chronic ocular hypertension mouse model by inducing intraocular pressure (IOP) elevation using a suture technique previously developed for rats. METHODS. C57BL/6 mice were given monocular circumlimbal suture (10/0) placement under anesthesia (ketamine/xylazine). The suture was left in place for 12 weeks (n = 10). A control group had the same treatment while it was removed after day 1 (n = 10). Intraocular pressure, electroretinogram (ERG), and optical coherence tomography (OCT) were measured in both groups for 12 weeks. At week 12, animals were euthanized and retina was harvested for histologic assessment. RESULTS. In the group with extended suture placement, IOP spiked from 14.3 ± 0.9 to 48.4 ± 4.8 mm Hg immediately after suture implantation. At day 1, it declined to 33.2 ± 3.7 mm Hg and remained elevated for 12 weeks. In the suture removal group, IOP normalized to baseline within a day following suture removal. In the group with prolonged IOP elevation, the retinal ganglion cell (RGC) mediated ERG responses continued to exacerbate and were significantly reduced by week 12 (P < 0.001). Progressive loss of retinal nerve fiber layer was found and it became significant from week 4 (P < 0.001). At week 12, significant loss of RGCs (P < 0.001) was noted. In the IOP normalization group, no alteration in ERG, OCT, and RGC counting was observed. CONCLUSIONS. The circumlimbal suture approach produces a mild chronic IOP elevation in mice. Functional and structural changes under model induction are largely independent of the initial IOP spike. © 2017, Association for Research in Vision and Ophthalmology Inc. All rights reserved.

DOI10.1167/iovs.16-20576