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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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Affected ganglion cells labeled with the gene gun or SMI32 immunostaining. (A and B) Affected ganglion cells show a loss of second and higher order dendrites. Only a few and short third order dendrites are visible (arrows). (C and D) These ganglion cells sometimes have long, tortuous dendrites that course in spirals through a considerable portion of the IPL, appearing as loops in the projection image (arrowheads). (E and F) In severely affected ganglion cells, only the cell body and the proximal part of the primary dendrites are visible. (G and H) An affected (G) cell body from a diseased DBA/2J retina (nerve grade severe) at high resolution and a normal SMI32 cell (H) for comparison. SMI32 staining (green), ChAT staining (red), and nuclei staining (blue) are shown. (I and J) The same cells at lower magnification with the dendrites in focus. (K and L) Neighboring cells. Note the loss of SMI32+ cells for the severely affected retina in F. Bars: (A–F) 100 μm; (G and H) 20 μm; (I–L) 100 μm.
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fig4: Affected ganglion cells labeled with the gene gun or SMI32 immunostaining. (A and B) Affected ganglion cells show a loss of second and higher order dendrites. Only a few and short third order dendrites are visible (arrows). (C and D) These ganglion cells sometimes have long, tortuous dendrites that course in spirals through a considerable portion of the IPL, appearing as loops in the projection image (arrowheads). (E and F) In severely affected ganglion cells, only the cell body and the proximal part of the primary dendrites are visible. (G and H) An affected (G) cell body from a diseased DBA/2J retina (nerve grade severe) at high resolution and a normal SMI32 cell (H) for comparison. SMI32 staining (green), ChAT staining (red), and nuclei staining (blue) are shown. (I and J) The same cells at lower magnification with the dendrites in focus. (K and L) Neighboring cells. Note the loss of SMI32+ cells for the severely affected retina in F. Bars: (A–F) 100 μm; (G and H) 20 μm; (I–L) 100 μm.

Mentions: Some of the cells in affected retinas had clearly abnormal morphology (Fig. 4, A–F). Although their numbers varied from retina to retina, they were a constant feature of all but the most lightly affected tissues. The dendrites of affected cells appeared underbranched. Only primary and secondary dendrites are visible, whereas the higher order branches, usually present on these cells, are lost. Another feature of these cells was the appearance of contorted dendrites that seem to loop and fold back (Fig. 4, C and D, arrowheads), shapes that are never observed in normal ganglion cells. In the most severe cases, only the primary dendrites—sometimes only their proximal segments—were still visible.


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)

Affected ganglion cells labeled with the gene gun or SMI32 immunostaining. (A and B) Affected ganglion cells show a loss of second and higher order dendrites. Only a few and short third order dendrites are visible (arrows). (C and D) These ganglion cells sometimes have long, tortuous dendrites that course in spirals through a considerable portion of the IPL, appearing as loops in the projection image (arrowheads). (E and F) In severely affected ganglion cells, only the cell body and the proximal part of the primary dendrites are visible. (G and H) An affected (G) cell body from a diseased DBA/2J retina (nerve grade severe) at high resolution and a normal SMI32 cell (H) for comparison. SMI32 staining (green), ChAT staining (red), and nuclei staining (blue) are shown. (I and J) The same cells at lower magnification with the dendrites in focus. (K and L) Neighboring cells. Note the loss of SMI32+ cells for the severely affected retina in F. Bars: (A–F) 100 μm; (G and H) 20 μm; (I–L) 100 μm.
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Related In: Results  -  Collection

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fig4: Affected ganglion cells labeled with the gene gun or SMI32 immunostaining. (A and B) Affected ganglion cells show a loss of second and higher order dendrites. Only a few and short third order dendrites are visible (arrows). (C and D) These ganglion cells sometimes have long, tortuous dendrites that course in spirals through a considerable portion of the IPL, appearing as loops in the projection image (arrowheads). (E and F) In severely affected ganglion cells, only the cell body and the proximal part of the primary dendrites are visible. (G and H) An affected (G) cell body from a diseased DBA/2J retina (nerve grade severe) at high resolution and a normal SMI32 cell (H) for comparison. SMI32 staining (green), ChAT staining (red), and nuclei staining (blue) are shown. (I and J) The same cells at lower magnification with the dendrites in focus. (K and L) Neighboring cells. Note the loss of SMI32+ cells for the severely affected retina in F. Bars: (A–F) 100 μm; (G and H) 20 μm; (I–L) 100 μm.
Mentions: Some of the cells in affected retinas had clearly abnormal morphology (Fig. 4, A–F). Although their numbers varied from retina to retina, they were a constant feature of all but the most lightly affected tissues. The dendrites of affected cells appeared underbranched. Only primary and secondary dendrites are visible, whereas the higher order branches, usually present on these cells, are lost. Another feature of these cells was the appearance of contorted dendrites that seem to loop and fold back (Fig. 4, C and D, arrowheads), shapes that are never observed in normal ganglion cells. In the most severe cases, only the primary dendrites—sometimes only their proximal segments—were still visible.

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