title: A novel rodent model of posterior ischemic optic neuropathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Dale P
authors.initials: DP
authors.lastname: Brown
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Duan
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Brant D
authors.initials: BD
authors.lastname: Watson
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002199:Capillary Permeability; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D007511:Ischemia / Q000150:complications / Q000378:metabolism; D053844:Lasers, Solid-State; D008297:Male; D017628:Microglia / Q000473:pathology; D009410:Nerve Degeneration / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D009900:Optic Nerve / Q000098:blood supply / Q000473:pathology; D020221:Optic Nerve Injuries / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D018917:Optic Neuropathy, Ischemic / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D013266:Stilbamidines / Q000378:metabolism
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D003911:Dextrans; D013266:Stilbamidines; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate
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