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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 mount of a severely affected retina with virtually no remaining ganglion cells. (A) High-resolution survey of a whole-mounted retina from one of the most severely affected eyes in our sample stained for SMI32 (green), ChAT (red), and counterstained with TOPRO (blue). Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Hardly any SMI32+ cells or axons are left. Remaining cells often show long, unbranched dendrites. The open arrowhead in D points to a blood vessel that has been unspecifically labeled by the secondary antibody. The closed arrowhead in B points to an anomalous SMI32+ cell. The arrows in C indicate remaining axons. Note that the ChAT+ cells (red) are unaffected. Bar, 100 μm.
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fig9: Whole mount of a severely affected retina with virtually no remaining ganglion cells. (A) High-resolution survey of a whole-mounted retina from one of the most severely affected eyes in our sample stained for SMI32 (green), ChAT (red), and counterstained with TOPRO (blue). Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Hardly any SMI32+ cells or axons are left. Remaining cells often show long, unbranched dendrites. The open arrowhead in D points to a blood vessel that has been unspecifically labeled by the secondary antibody. The closed arrowhead in B points to an anomalous SMI32+ cell. The arrows in C indicate remaining axons. Note that the ChAT+ cells (red) are unaffected. 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 mount of a severely affected retina with virtually no remaining ganglion cells. (A) High-resolution survey of a whole-mounted retina from one of the most severely affected eyes in our sample stained for SMI32 (green), ChAT (red), and counterstained with TOPRO (blue). Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Hardly any SMI32+ cells or axons are left. Remaining cells often show long, unbranched dendrites. The open arrowhead in D points to a blood vessel that has been unspecifically labeled by the secondary antibody. The closed arrowhead in B points to an anomalous SMI32+ cell. The arrows in C indicate remaining axons. Note that the ChAT+ cells (red) are unaffected. Bar, 100 μm.
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Related In: Results  -  Collection

Show All Figures
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fig9: Whole mount of a severely affected retina with virtually no remaining ganglion cells. (A) High-resolution survey of a whole-mounted retina from one of the most severely affected eyes in our sample stained for SMI32 (green), ChAT (red), and counterstained with TOPRO (blue). Bar, 500 μm. (B–E) High-power views of the boxed areas outlined in A. Hardly any SMI32+ cells or axons are left. Remaining cells often show long, unbranched dendrites. The open arrowhead in D points to a blood vessel that has been unspecifically labeled by the secondary antibody. The closed arrowhead in B points to an anomalous SMI32+ cell. The arrows in C indicate remaining axons. Note that the ChAT+ cells (red) are unaffected. 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