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Y. Guo, S. L. Bernstein; A Model of Optic Nerve Stroke (rAION) Selectively Results in an Isolated RGC Loss. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3065. doi: https://doi.org/.
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We recently introduced a rodent model of Non-arteritic ischemic optic neuropathy (rAION). We wanted to demonstrate that the optic nerve infarct and corresponding retinal lesion results in isolated retinal ganglion cell (RGC) death, and does not generate direct damage to other retinal neuronal cell types, that might be consistent with artery or vein occlusion. Since displaced amacrine neurons make up ~35% of the cells in the RGC layer, we evaluated potential changes in amacrine cell numbers following rAION.
We utilized a transgenic mouse containing cyan fluorescent protein (CFP) under control of a Thy-1 promoter that results in isolated RGC-CFP expression. rAION was induced as previously described (Bernstein et al, IOVS 2007). We utilized confocal immunohistochemical analysis, employing anti-choline acetyl transferase (ChAT) immunostaining to identify amacrine cells in the inner nuclear (INL) and RGC layers. 21 days post-induction, whole retina flat mount and retinal serial sections were evaluated. Stereological cell analysis was performed on whole mount retinae, comparing numbers of Thy-1-CFP (RGC) and ChAT (+) (amacrine) cells after rAION.
A total of 8 retinae were employed for whole mount immunofluorescent staining, and 3 animals in the retina serial section staining. Similar to our previous results, there were varying degrees of CFP (+) cell loss post-rAION. This rangs from 40-61% (mean= 51%) . The number of ChAT (+) amacrine cells remained relatively constant, ranging from 90% to 116% (mean=100%) in the RGC layer in rAION retinae compared with control.
Our data demonstrate that the rAION model results in isolated RGC death in the RGC layer, leaving amacrine cell neurons in the same cell layer relatively unaffected. This suggests that isolated optic nerve ischemia results in a pure optic nerve lesion that directly affects RGCs. The subsequent RGC death does not cause associated amacrine cell loss either immediately, or at relatively later times.
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