A novel rodent model of posterior ischemic optic neuropathy

Yan Wang, Dale P. Brown, Yuanli Duan, Wei Kong, Brant D. Watson, Jeffrey L. Goldberg

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objectives: To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods: Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate-dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results: Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions: Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance: The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies.

Original languageEnglish
Pages (from-to)194-204
Number of pages11
JournalJAMA Ophthalmology
Volume131
Issue number2
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

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Ischemic Optic Neuropathy
Rodentia
Retinal Ganglion Cells
Optic Nerve
Ischemia
Optic Nerve Injuries
Ciliary Neurotrophic Factor
Optic Nerve Diseases
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Wounds and Injuries
Astrocytes
Hypertrophy
Blood Vessels
Retina
Edema
Cell Survival
Animal Models
Immunohistochemistry
Control Groups

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Wang, Y., Brown, D. P., Duan, Y., Kong, W., Watson, B. D., & Goldberg, J. L. (2013). A novel rodent model of posterior ischemic optic neuropathy. JAMA Ophthalmology, 131(2), 194-204. https://doi.org/10.1001/2013.jamaophthalmol.271

A novel rodent model of posterior ischemic optic neuropathy. / Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

In: JAMA Ophthalmology, Vol. 131, No. 2, 01.02.2013, p. 194-204.

Research output: Contribution to journalArticle

Wang, Y, Brown, DP, Duan, Y, Kong, W, Watson, BD & Goldberg, JL 2013, 'A novel rodent model of posterior ischemic optic neuropathy', JAMA Ophthalmology, vol. 131, no. 2, pp. 194-204. https://doi.org/10.1001/2013.jamaophthalmol.271
Wang Y, Brown DP, Duan Y, Kong W, Watson BD, Goldberg JL. A novel rodent model of posterior ischemic optic neuropathy. JAMA Ophthalmology. 2013 Feb 1;131(2):194-204. https://doi.org/10.1001/2013.jamaophthalmol.271
Wang, Yan ; Brown, Dale P. ; Duan, Yuanli ; Kong, Wei ; Watson, Brant D. ; Goldberg, Jeffrey L. / A novel rodent model of posterior ischemic optic neuropathy. In: JAMA Ophthalmology. 2013 ; Vol. 131, No. 2. pp. 194-204.
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