title: [Temporal and spatial characteristics of RGC death and axon degeneration in the rat model of nonarteritic anterior ischemic optic neuropathy].
abstract: Objective:To investigate the temporal and spatial characteristics of retinal ganglion cell (RGC) death and axon degeneration in the rat model of nonarteritic anterior ischemic optic neuropathy (rNAION).Methods:Experimental study. The model of rNAION was induced by directly illuminating the optic nerve head with laser, after intravenous infusion with the photosensitizing agent rose Bengal. Seventy-one SD rats were randomly divided into five groups: 1-week (n=14), 2-week (n=14), 4-week (n=15) , 8-week (n=16) model group and the normal control group (n=12). Hematoxylin and eosin (H&E) staining and morphometric measurement with FG labeling were performed to assess rNAION-indeced histologic changes in the retina at different time points. RGCs were counted on retinal flat mounts in a masked fashion. Semithin sections stained with toluidine blue and transmission electron microscopy were performed to evaluate axonal degeneration. The differences of RGC density among multiple groups were tested with one-way ANOVA while the survival rate of RGC with kruskal-Wallis.Results:H&E-stained retina sections of rNAION revealed RGC loss. The density of labeled RGC was (2 273±219) cells/mm2in the control group, (2 075±120) cells/mm2in the 1-week group, (1 783±143) cells/mm2in the 2-week group, (1 330±169) cells/mm2in the 4-week group and (869±301) cells/mm2in the 8-week group. There were significant differences between all pairs of groups (F=80.98,P<0.01). The impairment of RGC was aggravatedprogressively, which mainly in the upper quadrant. The survival rate of RGC was 99.9%±3.4%, 91.8%±2.9%, 72.6%±5.7%, 54.4%±7.0% and 37.5%±13.0%, respectively. There were significant differences between the 1-week and 2-week group(Z=-3.78, P<0.01), the 2-week and 4-week group(Z=-3.89, P<0.01), and the 4-week and 8-week group(Z=-3.23, P<0.01). Toluidine blue staining of the ON revealed significant demyelination 1 week after ischemic damage. Progressive axonal degeneration existed for several weeks, which mainly affected the central region of the optic nerve with extensive reactive gliosis. Ultrastructural study showed axonal edema and collapsed sheaths in the ischemic optic. Four weeks later, there were extensive axonal loss and severe glial scars.Conclusions:rNAION results in regional and later RGC death. The extended period of RGC death after rNAION induction is much more longer than previously recognized. (Chin J Ophthalmol,2016,52: 918-923).
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors.forename: Y W
authors.initials: YW
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: Y
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001369:Axons; D004195:Disease Models, Animal; D009389:Neovascularization, Pathologic; D009898:Optic Disk; D009900:Optic Nerve / Q000473:pathology*; D018917:Optic Neuropathy, Ischemic / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014792:Visual Acuity / Q000502:physiology