Establishment and assessment of a rat model of nonarteritic anterior ischemic optic neuropathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Yiwei , Chen Ting , Ma Jin ,  Zhong Yong

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China;

Corresponding author：

Zhong Yong, Email: yzhong_eye@163.com

Keywords：

Optic neuropathy, ischemic; Retinal ganglion cells; Disease models, animal

DOI：

10.3760/cma.j.issn.1005-1015.2018.01.015

Video：

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Objective To establish and evaluate a rat model of nonarteritic anterior ischemic optic neuropathy (NAION). Methods The rats were randomly divided into control group (n=13), sham laser group (n=11) and NAION group (n=23). The right eye was set as the experimental eye. NAION model was induced by directly illuminating the optic nerve (ON) of the right eye with 532 nm green laser, after intravenous infusion with the photosensitizing agent Rose Bengal. Sham laser treatment consisted of illuminating the ON region with 532 nm laser without Rose Bengal injection. Rats in control group underwent no intervention. The appearance of optic disc was observed with funduscope at 12 hours, 1, 3, 7, 28 days post-illumination. The histologic changes in the retina and ON of the NAION model were evaluated qualitatively with hematoxylin and eosin (HE) staining and transmission electron microscopy. The retrograde-labeled retinal ganglion cells (RGC) were counted on photographs taken from retinal flat mounts in a masked fashion. Results The optic disc in NAION eyes were swollen 3 days after photodynamic treatment. HE-stained longitudinal ON sections of NAION revealed vacuolar degeneration on day 3 after induction. Besides, ultrastructural study showed axonal edema and collapsed sheaths in the ischemic optic nerve at the same time point after modeling. ON edema resolved 7 days after induction. The final results revealed optic disc atrophy, extensive axonal loss, severe glial scar, and RGC death in large numbers 4 weeks after modeling. There were no aforementioned manifestations in control and sham laser group. The RGC density of the right eyes was statistically significantly lower in NAION group than that in control group and in sham laser group (t=−14.142, −14.088; P=0.000, 0.000). The survival rate of RGC was statistically significantly lower in NAION group than in control group and in sham laser group (t=−17.048, −16.667; P=0.000, 0.000). There was no difference of RGC density and survival rate of RGC between control and sham laser group (t=0.050, 0.348; P=0.961, 0.731). Conclusion A rat model of NAION was established successfully by photodynamic treatments with Rose Bengal, which induce optic nerve damage and RGC death.

Citation： Wang Yiwei, Chen Ting, Ma Jin, Zhong Yong. Establishment and assessment of a rat model of nonarteritic anterior ischemic optic neuropathy. Chinese Journal of Ocular Fundus Diseases, 2018, 34(1): 60-64. doi: 10.3760/cma.j.issn.1005-1015.2018.01.015 Copy

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2.	Bernstein SL, Johnson MA, Miller NR. Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models[J]. Prog Retin Eye Res, 2011, 30(3): 167-187. DOI: 10.1016/j.preteyeres.2011.02.003.
3.	Bernstein SL, Guo Y, Kelman SE, et al. Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2003, 44(10): 4153-4162. DOI: 10.1167/iovs.03-0274.
4.	王润生, 王小娣, 吕沛霖, 等. 光动力诱导前部缺血性视神经病变的实验研究[J]. 中华眼底病杂志, 2008, 24(2): 90-94.Wang RS, Wang XD, Lyu PL, et al. Experimental study on photodynamic induced anterior ischemic optic neuropathy in rat animals[J]. Chin J Ocul Fundus Dis, 2008, 24(2): 90-94.
5.	Ma J, Jiang L, Zhong Y, et al. Neuroprotective effect on retinal ganglion cells by transpupillary laser irradiation of the optic nerve head[J]. Neurosci Lett, 2010, 476(1): 3-8. DOI: 10.1016/j.neulet.2010.01.001.
6.	Ma K, Xu L, Zhang H, et al. Effect of brimonidine on retinal ganglion cell survival in an optic nerve crush model[J]. Am J Ophthalmol, 2009, 147(2): 326-331. DOI: 10.1016/j.ajo.2008.08.005.
7.	Sugiyama K, Gu ZB, Kawase C, et al. Optic nerve and peripapillary choroidal microvasculature of the rat eye[J]. Invest Ophthalmol Vis Sci, 1999, 40(13): 3084-3090.
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9.	Knox DL, Kerrison JB, Green WR. Histopathologic studies of ischemic optic neuropathy[J]. Trans Am Ophthalmol Soc, 2000, 98:203-222.
10.	Zhang C, Guo Y, Slater BJ, et al. Axonal degeneration, regeneration and ganglion cell death in a rodent model of anterior ischemic optic neuropathy (rAION)[J]. Exp Eye Res, 2010, 91(2): 286-292. DOI: 10.1016/j.exer.2010.05.021.
11.	Slater BJ, Mehrabian Z, Guo Y, et al. Rodent anterior ischemic optic neuropathy (rAION) induces regional retinal ganglion cell apoptosis with a unique temporal pattern[J]. Invest Ophthalmol Vis Sci, 2008, 49(8): 3671-3676. DOI: 10.1167/iovs.07-0504.
12.	Bernstein SL, Mehrabyan Z, Guo Y, et al. Estrogen is not neuroprotective in a rodent model of optic nerve stroke[J]. Mol Vis, 2007, 13:1920-1925.
13.	Schmid H, Renner M, Dick HB, et al. Loss of inner retinal neurons after retinal ischemia in rats[J]. Invest Ophthalmol Vis Sci, 2014, 55(4): 2777-2787. DOI: 10.1167/iovs.13-13372.
14.	Vidal-Sanz M, Salinas-Navarro M, Nadal-Nicolas FM, et al. Understanding glaucomatous damage: anatomical and functional data from ocular hypertensive rodent retinas[J]. Prog Retin Eye Res, 2012, 31(1): 1-27. DOI: 10.1016/j.preteyeres.2011.08.001.
15.	Sanchez-Migallon MC, Valiente-Soriano FJ, Nadal-Nicolas FM, et al. Apoptotic retinal ganglion cell death after optic nerve transection or crush in mice: delayed rgc loss with BDNF or a Caspase 3 inhibitor[J]. Invest Ophthalmol Vis Sci, 2016, 57(1): 81-93. DOI: 10.1167/iovs.15-17841.
16.	Parrilla-Reverter G, Agudo M, Nadal-Nicolas F, et al. Time-course of the retinal nerve fibre layer degeneration after complete intra-orbital optic nerve transection or crush: a comparative study[J]. Vision Res, 2009, 49(23): 2808-2825. DOI: 10.1016/j.visres.2009.08.020.
17.	Aktas Z, Gurelik G, Gocun PU, et al. Matrix metalloproteinase-9 expression in retinal ganglion cell layer and effect of topically applied brimonidine tartrate 0.2% therapy on this expression in an endothelin-1-induced optic nerve ischemia model[J]. Int Oph-thalmol, 2010, 30(3): 253-259. DOI: 10.1007/s10792-009-9316-9.

1. Miller NR. Current concepts in the diagnosis, pathogenesis, and management of nonarteritic anterior ischemic optic neuropathy[J]. J Neuroophthalmol, 2011, 31(2): 1-3. DOI: 10.1097/WNO.0b013e31821f955c.
2. Bernstein SL, Johnson MA, Miller NR. Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models[J]. Prog Retin Eye Res, 2011, 30(3): 167-187. DOI: 10.1016/j.preteyeres.2011.02.003.
3. Bernstein SL, Guo Y, Kelman SE, et al. Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2003, 44(10): 4153-4162. DOI: 10.1167/iovs.03-0274.
4. 王润生, 王小娣, 吕沛霖, 等. 光动力诱导前部缺血性视神经病变的实验研究[J]. 中华眼底病杂志, 2008, 24(2): 90-94.Wang RS, Wang XD, Lyu PL, et al. Experimental study on photodynamic induced anterior ischemic optic neuropathy in rat animals[J]. Chin J Ocul Fundus Dis, 2008, 24(2): 90-94.
5. Ma J, Jiang L, Zhong Y, et al. Neuroprotective effect on retinal ganglion cells by transpupillary laser irradiation of the optic nerve head[J]. Neurosci Lett, 2010, 476(1): 3-8. DOI: 10.1016/j.neulet.2010.01.001.
6. Ma K, Xu L, Zhang H, et al. Effect of brimonidine on retinal ganglion cell survival in an optic nerve crush model[J]. Am J Ophthalmol, 2009, 147(2): 326-331. DOI: 10.1016/j.ajo.2008.08.005.
7. Sugiyama K, Gu ZB, Kawase C, et al. Optic nerve and peripapillary choroidal microvasculature of the rat eye[J]. Invest Ophthalmol Vis Sci, 1999, 40(13): 3084-3090.
8. Hayreh SS. Ischemic optic neuropathy[J]. Prog Retin Eye Res, 2009, 28(1): 34-62. DOI: 10.1016/j.preteyeres.2008.11.002.
9. Knox DL, Kerrison JB, Green WR. Histopathologic studies of ischemic optic neuropathy[J]. Trans Am Ophthalmol Soc, 2000, 98:203-222.
10. Zhang C, Guo Y, Slater BJ, et al. Axonal degeneration, regeneration and ganglion cell death in a rodent model of anterior ischemic optic neuropathy (rAION)[J]. Exp Eye Res, 2010, 91(2): 286-292. DOI: 10.1016/j.exer.2010.05.021.
11. Slater BJ, Mehrabian Z, Guo Y, et al. Rodent anterior ischemic optic neuropathy (rAION) induces regional retinal ganglion cell apoptosis with a unique temporal pattern[J]. Invest Ophthalmol Vis Sci, 2008, 49(8): 3671-3676. DOI: 10.1167/iovs.07-0504.
12. Bernstein SL, Mehrabyan Z, Guo Y, et al. Estrogen is not neuroprotective in a rodent model of optic nerve stroke[J]. Mol Vis, 2007, 13:1920-1925.
13. Schmid H, Renner M, Dick HB, et al. Loss of inner retinal neurons after retinal ischemia in rats[J]. Invest Ophthalmol Vis Sci, 2014, 55(4): 2777-2787. DOI: 10.1167/iovs.13-13372.
14. Vidal-Sanz M, Salinas-Navarro M, Nadal-Nicolas FM, et al. Understanding glaucomatous damage: anatomical and functional data from ocular hypertensive rodent retinas[J]. Prog Retin Eye Res, 2012, 31(1): 1-27. DOI: 10.1016/j.preteyeres.2011.08.001.
15. Sanchez-Migallon MC, Valiente-Soriano FJ, Nadal-Nicolas FM, et al. Apoptotic retinal ganglion cell death after optic nerve transection or crush in mice: delayed rgc loss with BDNF or a Caspase 3 inhibitor[J]. Invest Ophthalmol Vis Sci, 2016, 57(1): 81-93. DOI: 10.1167/iovs.15-17841.
16. Parrilla-Reverter G, Agudo M, Nadal-Nicolas F, et al. Time-course of the retinal nerve fibre layer degeneration after complete intra-orbital optic nerve transection or crush: a comparative study[J]. Vision Res, 2009, 49(23): 2808-2825. DOI: 10.1016/j.visres.2009.08.020.
17. Aktas Z, Gurelik G, Gocun PU, et al. Matrix metalloproteinase-9 expression in retinal ganglion cell layer and effect of topically applied brimonidine tartrate 0.2% therapy on this expression in an endothelin-1-induced optic nerve ischemia model[J]. Int Oph-thalmol, 2010, 30(3): 253-259. DOI: 10.1007/s10792-009-9316-9.

Chinese Journal of Ocular Fundus Diseases

Establishment and assessment of a rat model of nonarteritic anterior ischemic optic neuropathy

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