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T. C. Jakobs, D. Sun, M. Lye-Barthel, R. H. Masland; The Spatial Arrangement of Astrocytes in the Glial Lamina of the Mouse. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4316.
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A mouse model of inherited glaucoma (DBA/2J) presents with a characteristic sectorial loss of retinal ganglion cells (Jakobs et al., 2005). Mice do not have a collagenous lamina cribrosa, yet evidence points to an astrocyte-rich region in the unmyelinated part of the optic nerve directly behind the globe (the glial lamina) as the site of axonal insult (Howell et al., 2007). In this region astrocytes ensheath ganglion cell axons to form discrete bundles, and damage to these bundles may explain the sectorial loss of ganglion cells. We investigated the spatial relationship between individual optic nerve astrocytes and the axon bundles.
We used transgenic mouse lines expressing (1) GFP in subsets of astrocytes (hGFAPpr-GFP), or (2) GFP or DsRed in ganglion cells and their axons. Additionally, several markers (GFAP, MBP, S100, NG2, connexins) were studied within these mice lines using immunohistochemistry followed by confocal microscopy. Individual cells were also labeled by dye injection or particle-mediated dye transfer.
The domains of astrocytes in the glial lamina do not tile: processes of single astrocytes within the glial lamina can span the entire diameter of the nerve. Because they are numerous (~ 200 astrocytes in the glial lamina, which is ~ 0.004 mm3 in volume) they overlap substantially, and each astrocyte participates in forming the sheaths of at least one third of the axon bundles, both adjacent and distant. Conversely, each glial sheath in the honeycomb structure contains processes of ~ 9 individual astrocytes.
The distributed nature of the astrocytic matrix makes it difficult to explain the focal damage to axon bundles by a focal deleterious (or supportive) action of the ensheathing astrocytes. The difficulty is compounded by numerous gap junctions among processes of the overlapping astrocytes.
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