Neurosurgical Modeling of Retinal Ischemia-Reperfusion Injury

Alireza P Shabanzadeh; Philippe M D'Onofrio; Philippe P Monnier; Paulo D Koeberle

doi:10.1016/j.jstrokecerebrovasdis.2017.10.019

Neurosurgical Modeling of Retinal Ischemia-Reperfusion Injury

J Stroke Cerebrovasc Dis. 2018 Apr;27(4):845-856. doi: 10.1016/j.jstrokecerebrovasdis.2017.10.019. Epub 2017 Nov 29.

Authors

Alireza P Shabanzadeh¹, Philippe M D'Onofrio², Philippe P Monnier³, Paulo D Koeberle⁴

Affiliations

¹ Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
² Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Rehabilitation Science Institute, University of Toronto, Toronto, Ontario, Canada.
³ Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
⁴ Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Rehabilitation Science Institute, University of Toronto, Toronto, Ontario, Canada. Electronic address: paulo.koeberle@utoronto.ca.

PMID: 29196198
DOI: 10.1016/j.jstrokecerebrovasdis.2017.10.019

Abstract

Background: A reliable model of ischemia-reperfusion is required to evaluate the efficacy and safety of neuroprotective therapies for stroke. We present a novel reproducible pterygopalatine-ophthalmic artery ligation model of ischemia-reperfusion injury in the retina.

Methods: Rats were subjected to ophthalmic artery/meningeal sheath ligation (OAML-standard method) or clamping of the pterygopalatine-ophthalmic artery (OAC-new method) for 30 minutes. Retinal ganglion cell (RGC) survival was assessed by prelabeling with FluoroGold (FG) (Santa Cruz Biotechnology, CA, USA) and RNA-binding protein with multiple splicing (RBPMS) at 14 days after ischemia, and all results were compared with a sham group (n = 7 in each group).

Results: RGC density in the normal-uninjured (FG-labeled) group was 2111 ± 38 cells/mm² (mean ± standard error of mean) and that in the RBPMS-labeled group was 2142 ± 35 cells/mm². The OAML procedure significantly reduced RGC density to 738 ± 23 cells/mm² and 780 ± 41 cells/mm² (P < .001) in the FG-labeled and RBPMS-labeled groups, respectively. Similarly, OAC reduced RGC survival to 782 ± 19 cells/mm² and 813 ± 22 cells/mm² (P < .001) in the FG-labeled and RBPMS-labeled groups, respectively. RGC survival was similar following OAC and OAML models, suggesting that both induce comparable levels of damage. However, RGC survival in the OAC model was found to have less dispersion than OAML-induced ischemia.

Conclusions: These results suggest that the OAC procedure is a reliable reproduction of ischemia-reperfusion injury that mimics the effects of ophthalmic artery occlusion in humans and provides a useful research model for testing manipulations directed against pathways involved in RGC ischemic degeneration.

Keywords: Retina; ischemia; ophthalmic artery; reperfusion; retinal ganglion cell.

MeSH terms

Animals
Biomarkers / metabolism
Cell Survival
Constriction
Disease Models, Animal
Female
Ligation
Neurosurgical Procedures*
Ophthalmic Artery / physiopathology
Ophthalmic Artery / surgery*
RNA-Binding Proteins / metabolism
Rats, Sprague-Dawley
Regional Blood Flow
Reperfusion Injury / etiology*
Reperfusion Injury / pathology
Reperfusion Injury / physiopathology
Retinal Ganglion Cells / metabolism
Retinal Ganglion Cells / pathology*
Time Factors

Substances

Biomarkers
RNA-Binding Proteins