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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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Gallery of ganglion cell types encountered in glaucomatous DBA/2J. Individual ganglion cells were labeled either by biolistic delivery of FITC-dextran or by photodynamics. Images represent maximum-intensity projections of 20 confocal sections taken at 1-μm step size. Cells were from moderately or severely affected retinas (based on nerve grade). According to the classification by Sun et al. (2002a), the cells would be classified as follows: (A) type C4; (B) type A2 outer; (C) type C2 inner; (D) type B4; (E) type C5; (F) type B2; (G) type D2 (this cell is bistratified); (H) type A2 inner; (I) type C1; (J) type C2 outer; (K) type C5; and (L) type A1. Bars, 100 μm.
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fig3: Gallery of ganglion cell types encountered in glaucomatous DBA/2J. Individual ganglion cells were labeled either by biolistic delivery of FITC-dextran or by photodynamics. Images represent maximum-intensity projections of 20 confocal sections taken at 1-μm step size. Cells were from moderately or severely affected retinas (based on nerve grade). According to the classification by Sun et al. (2002a), the cells would be classified as follows: (A) type C4; (B) type A2 outer; (C) type C2 inner; (D) type B4; (E) type C5; (F) type B2; (G) type D2 (this cell is bistratified); (H) type A2 inner; (I) type C1; (J) type C2 outer; (K) type C5; and (L) type A1. Bars, 100 μm.

Mentions: In addition, we used the gene gun for biolistic delivery of dye-labeled dextrans to the retina. A total of 109 cells were labeled using rhodamine- or FITC-labeled gene gun bullets. Out of these cells, 46 were from moderately to very severely affected retinas and the remainder were from cases in which little or no cell loss was detectable. We saw no evidence for a preponderance of one or a few types in affected retinas, as would have occurred in the case of one or more resistant types. Fig. 3 shows a series of examples of ganglion cells in our sample.


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)

Gallery of ganglion cell types encountered in glaucomatous DBA/2J. Individual ganglion cells were labeled either by biolistic delivery of FITC-dextran or by photodynamics. Images represent maximum-intensity projections of 20 confocal sections taken at 1-μm step size. Cells were from moderately or severely affected retinas (based on nerve grade). According to the classification by Sun et al. (2002a), the cells would be classified as follows: (A) type C4; (B) type A2 outer; (C) type C2 inner; (D) type B4; (E) type C5; (F) type B2; (G) type D2 (this cell is bistratified); (H) type A2 inner; (I) type C1; (J) type C2 outer; (K) type C5; and (L) type A1. Bars, 100 μm.
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Related In: Results  -  Collection

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fig3: Gallery of ganglion cell types encountered in glaucomatous DBA/2J. Individual ganglion cells were labeled either by biolistic delivery of FITC-dextran or by photodynamics. Images represent maximum-intensity projections of 20 confocal sections taken at 1-μm step size. Cells were from moderately or severely affected retinas (based on nerve grade). According to the classification by Sun et al. (2002a), the cells would be classified as follows: (A) type C4; (B) type A2 outer; (C) type C2 inner; (D) type B4; (E) type C5; (F) type B2; (G) type D2 (this cell is bistratified); (H) type A2 inner; (I) type C1; (J) type C2 outer; (K) type C5; and (L) type A1. Bars, 100 μm.
Mentions: In addition, we used the gene gun for biolistic delivery of dye-labeled dextrans to the retina. A total of 109 cells were labeled using rhodamine- or FITC-labeled gene gun bullets. Out of these cells, 46 were from moderately to very severely affected retinas and the remainder were from cases in which little or no cell loss was detectable. We saw no evidence for a preponderance of one or a few types in affected retinas, as would have occurred in the case of one or more resistant types. Fig. 3 shows a series of examples of ganglion cells in our sample.

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