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Abstract #27207 Published in IGR 12-4
The development of new glaucoma mice model with the obstruction of axonal flow
Nakazawa T; Ryu M; Ahmed SNeuroscience Research 2010; 68
Purpose: Retinal ganglion cell (RGC) death is involved in the various retinal disorders, including glaucoma, diabetic retinopathy and vessel occlusion. Establishment of the neuroprotective treatment is an important strategy for the prevention of blindness. Evidences suggest that axonal damage is involved in the pathogenesis of glaucoma due to the deformity of lamina cribrosa and the ischemic insult in the optic nerve head. The purpose of this study is to develop the mice model of glaucoma with the disturbed axonal flow without the elevation of intraocular pressure (IOP). Methods: Adult male C57/BL6 mice were used in this study. To investigate the role of axonal damage in glaucoma-induced RGC death, we performed the optic nerve crush (NC) with forceps for 10 s or leaving the Spongel around the optic nerve soaked with vinblastine (0.1 to 10 mM), a microtubule disassembly drug. Obstruction of axonal flow was demonstrated by sequential retrograde labeling with fluorogold (FG) and DiI. To investigate the causative roles of the axonal flow obstruction and RGC death, RGC was labeled by FG and counted the density of survival RGCs 3, 5, 7, 10, and 14 days after injury. Results: Both of NC and vinblastine induced axonal damage demonstrated by the discontinuous immunoreactivity of neurofilament on the longitudinal section of optic nerve and the suppression of retrograde transport of FG. The density of surviving RGCs was significantly decreased more than 1mM of vinblastine 7 days after injury in a dose-dependent manner. By day 3 after injury, the density of surviving RGCs began to decrease significantly and, by day 7 and 28, almost 80% of RGCs were lost. BDNF and Tat-BH4, an inhibitor of mitochondrial activation, partially prevented the NC-induced RGC death. Conclusions: The obstruction of axonal flow in optic nerve had a causative role on the RGC death. This mice model is valuable for the research on the glaucoma especially normal tension glaucoma.
T. Nakazawa. Department of Ophthalmology, Tohoku University, Graduate School of Medicine, Japan.
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)