Limits...
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.

Show MeSH

Related in: MedlinePlus

Low-power views of the whole-mounted retina 1 wk after injection of rhodamine-dextran into the superior colliculus. The indicated severity refers to optic nerve grade. (A) Typical result in a nondiseased DBA/2J retina. A large, contiguous portion of the surface area is labeled with backfilled cells, which are barely distinguishable at this magnification as individual white dots. Bar, 500 μm. (B) Retina with moderate glaucoma. Two sectors of numerous brightly labeled cells (top right quadrant and bottom left quadrant, top) and less dense smaller sectors (bottom right quadrant) are visible. (C) Retina with severe cell loss. One narrow sector of labeled cells can be clearly seen in the bottom right quadrant. The density of backfilled cells is much lower than in A and B. The optic nerve head is marked by an asterisk. (D) High-resolution view of the boxed area outlined in C. Closed arrowheads point to axons, and open arrowheads indicate two individual backfilled cells whose dendrites are visible even at this magnification. (E) One of the most severely affected retinas in our sample. Hardly any backfilled cells are seen. A tenuous streak of backfilled cells courses from the optic nerve head (asterisk) to the four o'clock position. Another similar streak is visible in the top left quadrant (arrows). (F) High-resolution view of the boxed area outlined in E. The total number of labeled cells in this sector was low (<30), and most cells did not accumulate enough rhodamine-dextran granules to reveal their dendritic morphology. The arrows are the same as in E.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2171185&req=5

fig5: Low-power views of the whole-mounted retina 1 wk after injection of rhodamine-dextran into the superior colliculus. The indicated severity refers to optic nerve grade. (A) Typical result in a nondiseased DBA/2J retina. A large, contiguous portion of the surface area is labeled with backfilled cells, which are barely distinguishable at this magnification as individual white dots. Bar, 500 μm. (B) Retina with moderate glaucoma. Two sectors of numerous brightly labeled cells (top right quadrant and bottom left quadrant, top) and less dense smaller sectors (bottom right quadrant) are visible. (C) Retina with severe cell loss. One narrow sector of labeled cells can be clearly seen in the bottom right quadrant. The density of backfilled cells is much lower than in A and B. The optic nerve head is marked by an asterisk. (D) High-resolution view of the boxed area outlined in C. Closed arrowheads point to axons, and open arrowheads indicate two individual backfilled cells whose dendrites are visible even at this magnification. (E) One of the most severely affected retinas in our sample. Hardly any backfilled cells are seen. A tenuous streak of backfilled cells courses from the optic nerve head (asterisk) to the four o'clock position. Another similar streak is visible in the top left quadrant (arrows). (F) High-resolution view of the boxed area outlined in E. The total number of labeled cells in this sector was low (<30), and most cells did not accumulate enough rhodamine-dextran granules to reveal their dendritic morphology. The arrows are the same as in E.

Mentions: We injected seven 1-yr-old DBA/2J mice, one 2-mo-old DBA/2J mouse, and one C57BL/6J mouse bilaterally into the superior colliculi with rhodamine-dextran and imaged the retinas 1 wk later (Fig. 5). Out of 13 retinas studied, 12 had ganglion cells that contained rhodamine-dextran granules. Four of these retinas were normal. The other nine were moderately to severely affected. As described in the “Types of surviving ganglion cells” section, many of the ganglion cells had normal retrograde transport and normal morphology in the affected retinas. In contrast, those ganglion cells that had abnormal morphology were never seen to contain rhodamine-dextran granules from retrograde transport, indicating that retrograde transport was compromised. Furthermore, the axons of the abnormal ganglion cells appeared shrunken. In normal ganglion cells, the axons are readily visible after retrograde transport of fluorescent tracers or (especially) after staining of neurofilaments with the SMI32 antibody. In the ganglion cells with remodeled dendrites, the axons were clearly visible only near their exit from the soma; elsewhere, they were so thin as to be virtually invisible.


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)

Low-power views of the whole-mounted retina 1 wk after injection of rhodamine-dextran into the superior colliculus. The indicated severity refers to optic nerve grade. (A) Typical result in a nondiseased DBA/2J retina. A large, contiguous portion of the surface area is labeled with backfilled cells, which are barely distinguishable at this magnification as individual white dots. Bar, 500 μm. (B) Retina with moderate glaucoma. Two sectors of numerous brightly labeled cells (top right quadrant and bottom left quadrant, top) and less dense smaller sectors (bottom right quadrant) are visible. (C) Retina with severe cell loss. One narrow sector of labeled cells can be clearly seen in the bottom right quadrant. The density of backfilled cells is much lower than in A and B. The optic nerve head is marked by an asterisk. (D) High-resolution view of the boxed area outlined in C. Closed arrowheads point to axons, and open arrowheads indicate two individual backfilled cells whose dendrites are visible even at this magnification. (E) One of the most severely affected retinas in our sample. Hardly any backfilled cells are seen. A tenuous streak of backfilled cells courses from the optic nerve head (asterisk) to the four o'clock position. Another similar streak is visible in the top left quadrant (arrows). (F) High-resolution view of the boxed area outlined in E. The total number of labeled cells in this sector was low (<30), and most cells did not accumulate enough rhodamine-dextran granules to reveal their dendritic morphology. The arrows are the same as in E.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171185&req=5

fig5: Low-power views of the whole-mounted retina 1 wk after injection of rhodamine-dextran into the superior colliculus. The indicated severity refers to optic nerve grade. (A) Typical result in a nondiseased DBA/2J retina. A large, contiguous portion of the surface area is labeled with backfilled cells, which are barely distinguishable at this magnification as individual white dots. Bar, 500 μm. (B) Retina with moderate glaucoma. Two sectors of numerous brightly labeled cells (top right quadrant and bottom left quadrant, top) and less dense smaller sectors (bottom right quadrant) are visible. (C) Retina with severe cell loss. One narrow sector of labeled cells can be clearly seen in the bottom right quadrant. The density of backfilled cells is much lower than in A and B. The optic nerve head is marked by an asterisk. (D) High-resolution view of the boxed area outlined in C. Closed arrowheads point to axons, and open arrowheads indicate two individual backfilled cells whose dendrites are visible even at this magnification. (E) One of the most severely affected retinas in our sample. Hardly any backfilled cells are seen. A tenuous streak of backfilled cells courses from the optic nerve head (asterisk) to the four o'clock position. Another similar streak is visible in the top left quadrant (arrows). (F) High-resolution view of the boxed area outlined in E. The total number of labeled cells in this sector was low (<30), and most cells did not accumulate enough rhodamine-dextran granules to reveal their dendritic morphology. The arrows are the same as in E.
Mentions: We injected seven 1-yr-old DBA/2J mice, one 2-mo-old DBA/2J mouse, and one C57BL/6J mouse bilaterally into the superior colliculi with rhodamine-dextran and imaged the retinas 1 wk later (Fig. 5). Out of 13 retinas studied, 12 had ganglion cells that contained rhodamine-dextran granules. Four of these retinas were normal. The other nine were moderately to severely affected. As described in the “Types of surviving ganglion cells” section, many of the ganglion cells had normal retrograde transport and normal morphology in the affected retinas. In contrast, those ganglion cells that had abnormal morphology were never seen to contain rhodamine-dextran granules from retrograde transport, indicating that retrograde transport was compromised. Furthermore, the axons of the abnormal ganglion cells appeared shrunken. In normal ganglion cells, the axons are readily visible after retrograde transport of fluorescent tracers or (especially) after staining of neurofilaments with the SMI32 antibody. In the ganglion cells with remodeled dendrites, the axons were clearly visible only near their exit from the soma; elsewhere, they were so thin as to be virtually invisible.

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