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Published in: Japanese Journal of Ophthalmology 5/2012

01-09-2012 | Laboratory Investigation

Rodent model of nonarteritic ischemic optic neuropathy and its electrophysiological evaluation

Authors: Hideki Chuman, Tomoyuki Maekubo, Takako Osako, Yu Kodama, Michitaka Ishiai, Nobuhisa Nao-i

Published in: Japanese Journal of Ophthalmology | Issue 5/2012

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Abstract

Purpose

Our aim was to establish a rodent model of nonarteritic ischemic optic neuropathy (rNAION).

Methods

To induce rNAION, after administration of Rose Bengal (RB) (2.5 mM), the small vessels of the left optic nerve were photoactivated using a 514-nm argon green laser with about 500-μm spot size for 12 s (RB-laser induction). To evaluate the induction, funduscopic examination, fluorescein angiography (FA), visualization of capillaries within the optic disc, histologic evaluation, and electrophysiological testing were performed.

Results

In the RB-laser-induction eyes, the optic disc became swollen on day 3 followed by atrophy on week 8. FA showed filling defects in the choroid and optic disc at an early stage, followed by hyperfluorescence at a late stage. The capillaries within the optic disc were reduced markedly. Histopathologic examination showed acellular nerve fiber layer (NFL) swelling anterior to the optic disc. The morphologic retinal changes were apparent only in the retinal ganglion cell (RGC) layer, with a reduction in the number of cells. Visually evoked potential (VEP) amplitude decreased significantly, but electroretinography (ERG) showed no significant difference. The positive scotopic threshold response (pSTR) was not reduced on the 1st day but was significantly reduced 3 days after induction.

Conclusions

The findings are similar to human NAION. Therefore, RB-laser induction is well suited to establish the presence of rNAION.
Literature
1.
go back to reference Arnold AC. Ischemic optic neuropathy. In: Miller NR, Newman NJ, editors. Walsh & Hoyt’s clinical neuro-ophthalmology. Philadelphia: Lippincott Williams &Wilkins; 2005. p. 349–84. Arnold AC. Ischemic optic neuropathy. In: Miller NR, Newman NJ, editors. Walsh & Hoyt’s clinical neuro-ophthalmology. Philadelphia: Lippincott Williams &Wilkins; 2005. p. 349–84.
2.
go back to reference The Ischemic Optic Neuropathy Decompression Trial Research Group. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA. 1995;273:625–32.CrossRef The Ischemic Optic Neuropathy Decompression Trial Research Group. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA. 1995;273:625–32.CrossRef
3.
go back to reference Kelman SE. Intravitral triamcinolone or bevacizumab for nonarteritic anterior ischemic optic neuropathy: do they merit further study? J Neuroophthalmol. 2007;3:161–3.CrossRef Kelman SE. Intravitral triamcinolone or bevacizumab for nonarteritic anterior ischemic optic neuropathy: do they merit further study? J Neuroophthalmol. 2007;3:161–3.CrossRef
4.
go back to reference Bernstein SL, Guo Y, Kelman SE, Kelman SE, Flower RW, Johnson MA. Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2003;44:4153–62.PubMedCrossRef Bernstein SL, Guo Y, Kelman SE, Kelman SE, Flower RW, Johnson MA. Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2003;44:4153–62.PubMedCrossRef
5.
go back to reference Wang RS, Lv PL, Wang WJ, Wang XD, Zhang XJ, Li SN, et al. Establishing an experimental model of photodynamically induced anterior ischemic optic neuropathy. Vis Neurosci. 2011;28:155–62.PubMedCrossRef Wang RS, Lv PL, Wang WJ, Wang XD, Zhang XJ, Li SN, et al. Establishing an experimental model of photodynamically induced anterior ischemic optic neuropathy. Vis Neurosci. 2011;28:155–62.PubMedCrossRef
6.
go back to reference Bui BV, Fortune B. Ganglion cell contributions to the rat full-field electroretinogram. J Physiol. 2004;555:153–73.PubMedCrossRef Bui BV, Fortune B. Ganglion cell contributions to the rat full-field electroretinogram. J Physiol. 2004;555:153–73.PubMedCrossRef
7.
go back to reference Knox DL, Kerrison JB, Green WR. Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc. 2000;98:203–22.PubMed Knox DL, Kerrison JB, Green WR. Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc. 2000;98:203–22.PubMed
8.
go back to reference Masuzawa K, Jesmin S, Maeda S, Kaji Y, Oshika T, Zaedi S, et al. A model of retinal ischemia-reperfusion injury in rats by subconjunctival injection of endothelin-1. Exp Biol Med. 2006;231:1085–9. Masuzawa K, Jesmin S, Maeda S, Kaji Y, Oshika T, Zaedi S, et al. A model of retinal ischemia-reperfusion injury in rats by subconjunctival injection of endothelin-1. Exp Biol Med. 2006;231:1085–9.
9.
go back to reference Grozdanic SD, Sakaguchi DS, Kwon YH, Kardon RH, Sonea IM. Functional characterization of retina and optic nerve after acute ocular ischemia in rats. Invest Ophthalmol Vis Sci. 2003;44:2597–605.PubMedCrossRef Grozdanic SD, Sakaguchi DS, Kwon YH, Kardon RH, Sonea IM. Functional characterization of retina and optic nerve after acute ocular ischemia in rats. Invest Ophthalmol Vis Sci. 2003;44:2597–605.PubMedCrossRef
10.
go back to reference Duvdevani R, Rosner M, Belkin M, Sautter J, Sabel BA, Schwartz M. Graded crash of the rat optic nerve as a brain injury model: combining electrophysiological and behavioral outcome. Rest Neurol Neurosci. 1990;2:31–8. Duvdevani R, Rosner M, Belkin M, Sautter J, Sabel BA, Schwartz M. Graded crash of the rat optic nerve as a brain injury model: combining electrophysiological and behavioral outcome. Rest Neurol Neurosci. 1990;2:31–8.
11.
go back to reference Berkrlaar M, Clarke DB, Wang YC, Bray GM, Aguayo AJ. Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J Neurosci. 1994;14:4268–372. Berkrlaar M, Clarke DB, Wang YC, Bray GM, Aguayo AJ. Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J Neurosci. 1994;14:4268–372.
12.
go back to reference Bernstein SL, Johnson MA, Miller NR. Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models. Prog Retin Eye Res. 2011;30:167–87.PubMedCrossRef Bernstein SL, Johnson MA, Miller NR. Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models. Prog Retin Eye Res. 2011;30:167–87.PubMedCrossRef
13.
go back to reference Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985;17:497–504.PubMedCrossRef Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985;17:497–504.PubMedCrossRef
14.
go back to reference Zhao BQ, Suzuki Y, Kondo K, Kawano K, Ikeda Y, Umemura K. A novel MCA occulusion model of photothrombotic ischemia with cyclic flow reductions: development of cerebral hemorrhage induced by heparin. Brain Res Brain Res Protoc. 2002;9:85–92.PubMedCrossRef Zhao BQ, Suzuki Y, Kondo K, Kawano K, Ikeda Y, Umemura K. A novel MCA occulusion model of photothrombotic ischemia with cyclic flow reductions: development of cerebral hemorrhage induced by heparin. Brain Res Brain Res Protoc. 2002;9:85–92.PubMedCrossRef
15.
go back to reference Mosinger JL, Olney JW. Photothrombosis-induced ischemic neuronal degeneration in the rat retina. Exp Neurol. 1989;105:110–3.PubMedCrossRef Mosinger JL, Olney JW. Photothrombosis-induced ischemic neuronal degeneration in the rat retina. Exp Neurol. 1989;105:110–3.PubMedCrossRef
16.
go back to reference Fluhler EN, Hurley JK, Kochevar IE. Laser intensity and wavelength dependence of Rose Bengal- photosensitized inhibition of red blood cell acetylcholinesterase. Biochem Biophys Acta. 1994;990:269–75. Fluhler EN, Hurley JK, Kochevar IE. Laser intensity and wavelength dependence of Rose Bengal- photosensitized inhibition of red blood cell acetylcholinesterase. Biochem Biophys Acta. 1994;990:269–75.
17.
go back to reference Rodgers MAJ. Light-induced generation of signet oxygen in solutions of Rose Bengal. Chem Phys Lett. 1981;78:509–14.CrossRef Rodgers MAJ. Light-induced generation of signet oxygen in solutions of Rose Bengal. Chem Phys Lett. 1981;78:509–14.CrossRef
Metadata
Title
Rodent model of nonarteritic ischemic optic neuropathy and its electrophysiological evaluation
Authors
Hideki Chuman
Tomoyuki Maekubo
Takako Osako
Yu Kodama
Michitaka Ishiai
Nobuhisa Nao-i
Publication date
01-09-2012
Publisher
Springer Japan
Published in
Japanese Journal of Ophthalmology / Issue 5/2012
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-012-0167-y

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