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D. Sun, M. Lye-Barthel, R. H. Masland, T. C. Jakobs; Astrocytes of the Mouse Optic Nerve Head Segregate Ganglion Cell Axons Into Bundles. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3679. doi: https://doi.org/.
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A widely accepted explanation for the etiology of ganglion cell injury in glaucoma is mechanical. An abnormal intra-ocular pressure causes mechanical deformation of the lamina cribrosa - a sieve-like collagen plate at the optic nerve head - ultimately damaging the ganglion cell axons that pass through. One mouse strain (DBA/2J) develops glaucoma with a characteristic sectorial loss of ganglion cells and axons (Jakobs et al., 2005). However, rodents lack a lamina cribrosa and instead have a concentration of astrocytes in the unmyelinated portion of the optic nerve head (Morcos and Chan-Ling, 2000). The organization of astrocytes in this region is yet unknown. This study provides a detailed anatomical model of this region in the normal mouse for future comparison against the glaucomatous mouse.
Three different mouse lines were used: (1) wild type C57Bl/6; (2) a transgenic mouse expressing GFP in ganglion cells and their axons (YFP-12), and (3) a transgenic mouse expressing GFP in subsets of astrocytes (hGFAPpr-GFP). Additionally, the distribution of several markers (GFAP, MBP, Cx43) were studied within these mice lines using immunohistochemistry followed by confocal microscopy. DiI and DiO labeling was used to label axons.
The unmyelinated initial segment of the mouse optic nerve possesses a high concentration of astrocytes, apparently dominated by a single type that is oriented perpendicularly to the axis of the optic nerve. GFAP labeling of the YFP-12 mouse optic nerve showed that astrocytes in this region (but not in the myelinated part of the optic nerve) organize the ganglion cell axons into bundles, with each bundle corresponding to a specific sector of the retina. Astrocytes thus form "tubes" thorough which bundles of spatially related axons run. The astrocytes are heavily inter-connected by gap junctions expressing Cx43.
Astrocytes in the unmyelinated segment of the mouse optic nerve head form a ‘glial lamina’ (Howell et al., 2007; in press). There is structure within the glial lamina, such that bundles of related axons run together within a multi-glial ensheathment.
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