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Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice.

Jakobs TC, Libby RT, Ben Y, John SW, Masland RH - J. Cell Biol. (2005)

Bottom Line: Regions of cell death or survival radiated from the optic nerve head in fan-shaped sectors.Collectively, the data suggest axon damage at the optic nerve head as an early lesion, and damage to axon bundles would cause this pattern of degeneration.However, the architecture of the mouse eye seems to preclude a commonly postulated source of mechanical damage within the nerve head.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02114.

ABSTRACT
Using a variety of double and triple labeling techniques, we have reevaluated the death of retinal neurons in a mouse model of hereditary glaucoma. Cell-specific markers and total neuron counts revealed no cell loss in any retinal neurons other than the ganglion cells. Within the limits of our ability to define cell types, no group of ganglion cells was especially vulnerable or resistant to degeneration. Retrograde labeling and neurofilament staining showed that axonal atrophy, dendritic remodeling, and somal shrinkage (at least of the largest cell types) precedes ganglion cell death in this glaucoma model. Regions of cell death or survival radiated from the optic nerve head in fan-shaped sectors. Collectively, the data suggest axon damage at the optic nerve head as an early lesion, and damage to axon bundles would cause this pattern of degeneration. However, the architecture of the mouse eye seems to preclude a commonly postulated source of mechanical damage within the nerve head.

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Whole-mounted glaucomatous retina with persisting sectors of normal appearance. (A) High-resolution survey of a whole-mounted retina from a moderately affected retina stained for SMI32 (green) and ChAT (red) and counterstained with TOPRO (blue). The axon bundles entering the optic nerve head are markedly reduced and show sectors of relatively high axon densities alternating with sectors with almost no persisting axons. Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Bar, 100 μm.
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fig8: Whole-mounted glaucomatous retina with persisting sectors of normal appearance. (A) High-resolution survey of a whole-mounted retina from a moderately affected retina stained for SMI32 (green) and ChAT (red) and counterstained with TOPRO (blue). The axon bundles entering the optic nerve head are markedly reduced and show sectors of relatively high axon densities alternating with sectors with almost no persisting axons. Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Bar, 100 μm.

Mentions: This fan-shaped pattern of degeneration was further demonstrated by immunostaining of the whole-mount retinas with an antibody against SMI32. In normal retinas, the SMI32-positive axons completely surround the optic nerve head. In moderately severe disease, the axon bundles are noticeably thinned, and in the most extreme cases, the axons are almost completely lost (see Fig. 7 for a normal, Fig. 8 for an intermediary, and Fig. 9 for an extreme example). SMI32 also reveals that even in otherwise depleted retinas, a sector of almost normal appearance sometimes persists (see Fig. 10 for a striking example).


Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice.

Jakobs TC, Libby RT, Ben Y, John SW, Masland RH - J. Cell Biol. (2005)

Whole-mounted glaucomatous retina with persisting sectors of normal appearance. (A) High-resolution survey of a whole-mounted retina from a moderately affected retina stained for SMI32 (green) and ChAT (red) and counterstained with TOPRO (blue). The axon bundles entering the optic nerve head are markedly reduced and show sectors of relatively high axon densities alternating with sectors with almost no persisting axons. Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Bar, 100 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2171185&req=5

fig8: Whole-mounted glaucomatous retina with persisting sectors of normal appearance. (A) High-resolution survey of a whole-mounted retina from a moderately affected retina stained for SMI32 (green) and ChAT (red) and counterstained with TOPRO (blue). The axon bundles entering the optic nerve head are markedly reduced and show sectors of relatively high axon densities alternating with sectors with almost no persisting axons. Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Bar, 100 μm.
Mentions: This fan-shaped pattern of degeneration was further demonstrated by immunostaining of the whole-mount retinas with an antibody against SMI32. In normal retinas, the SMI32-positive axons completely surround the optic nerve head. In moderately severe disease, the axon bundles are noticeably thinned, and in the most extreme cases, the axons are almost completely lost (see Fig. 7 for a normal, Fig. 8 for an intermediary, and Fig. 9 for an extreme example). SMI32 also reveals that even in otherwise depleted retinas, a sector of almost normal appearance sometimes persists (see Fig. 10 for a striking example).

Bottom Line: Regions of cell death or survival radiated from the optic nerve head in fan-shaped sectors.Collectively, the data suggest axon damage at the optic nerve head as an early lesion, and damage to axon bundles would cause this pattern of degeneration.However, the architecture of the mouse eye seems to preclude a commonly postulated source of mechanical damage within the nerve head.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02114.

ABSTRACT
Using a variety of double and triple labeling techniques, we have reevaluated the death of retinal neurons in a mouse model of hereditary glaucoma. Cell-specific markers and total neuron counts revealed no cell loss in any retinal neurons other than the ganglion cells. Within the limits of our ability to define cell types, no group of ganglion cells was especially vulnerable or resistant to degeneration. Retrograde labeling and neurofilament staining showed that axonal atrophy, dendritic remodeling, and somal shrinkage (at least of the largest cell types) precedes ganglion cell death in this glaucoma model. Regions of cell death or survival radiated from the optic nerve head in fan-shaped sectors. Collectively, the data suggest axon damage at the optic nerve head as an early lesion, and damage to axon bundles would cause this pattern of degeneration. However, the architecture of the mouse eye seems to preclude a commonly postulated source of mechanical damage within the nerve head.

Show MeSH
Related in: MedlinePlus