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Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric.

Schlamp CL, Li Y, Dietz JA, Janssen KT, Nickells RW - BMC Neurosci (2006)

Bottom Line: Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe.Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region.Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA. clschlamp@wisc.edu

ABSTRACT

Background: Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal ganglion cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the betaGeo reporter gene, to evaluate the time course of optic nerve degeneration and ganglion cell loss, respectively, in aging mice.

Results: Optic nerve degeneration, characterized by axon loss and gliosis is first apparent in mice between 8 and 9 months of age. Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe. Although nerve damage is typically bilateral, the progression of disease is asymmetric between the eyes of individual mice. Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region. Ganglion cell loss, as a function of the loss of betaGeo expression, is evident in some mice between 8 and 10 months of age and is prevalent in the majority of mice older than 10.5 months. Most eyes display a uniform loss of ganglion cells throughout the retina, but many younger mice exhibit focal loss of cells in sectors extending from the optic nerve head to the retinal periphery. Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal.

Conclusion: A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma.

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Photomicrographs of the optic nerves of 3 mice labeled post-mortem with DiI. The images shown are dorsal views, looking down on the mouse head with the nose of the mouse facing the bottom of the image. The right nerve is on the left of each photomicrograph. (A) A young mouse (6 months of age) showing both optic nerves labeled from the globes to the optic chiasm. (B) An old mouse (10 months of age) showing relatively symmetric degeneration of both nerves. Degenerating nerves typically exhibit reduced label distally. (C) A second mouse at 10 months of age, showing asymmetric degeneration of it optic nerves. Only the left nerve is labeled. Bar = 0.5 mm.
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Figure 1: Photomicrographs of the optic nerves of 3 mice labeled post-mortem with DiI. The images shown are dorsal views, looking down on the mouse head with the nose of the mouse facing the bottom of the image. The right nerve is on the left of each photomicrograph. (A) A young mouse (6 months of age) showing both optic nerves labeled from the globes to the optic chiasm. (B) An old mouse (10 months of age) showing relatively symmetric degeneration of both nerves. Degenerating nerves typically exhibit reduced label distally. (C) A second mouse at 10 months of age, showing asymmetric degeneration of it optic nerves. Only the left nerve is labeled. Bar = 0.5 mm.

Mentions: A cohort of 270 nerves from 135 D2 mice, aged between 6 and 22.5 months, was used in this analysis. Mice were euthanized and the nerves labeled with DiI as described in the methods. Figure 1 shows examples of labeling from young (Fig. 1A) and aged mice (Figs. 1B and 1C). Young mice typically showed robust DiI labeling extending to the optic chiasm. Mice that exhibited degeneration of their nerves typically fell into the general categories of those showing symmetric (Fig. 1B) or asymmetric degeneration (Fig. 1C). In this latter group, some mice exhibited one relatively healthy appearing nerve and nearly complete loss of staining in the other. Further evaluation of the asymmetry of degeneration in these mice is presented below.


Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric.

Schlamp CL, Li Y, Dietz JA, Janssen KT, Nickells RW - BMC Neurosci (2006)

Photomicrographs of the optic nerves of 3 mice labeled post-mortem with DiI. The images shown are dorsal views, looking down on the mouse head with the nose of the mouse facing the bottom of the image. The right nerve is on the left of each photomicrograph. (A) A young mouse (6 months of age) showing both optic nerves labeled from the globes to the optic chiasm. (B) An old mouse (10 months of age) showing relatively symmetric degeneration of both nerves. Degenerating nerves typically exhibit reduced label distally. (C) A second mouse at 10 months of age, showing asymmetric degeneration of it optic nerves. Only the left nerve is labeled. Bar = 0.5 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1621073&req=5

Figure 1: Photomicrographs of the optic nerves of 3 mice labeled post-mortem with DiI. The images shown are dorsal views, looking down on the mouse head with the nose of the mouse facing the bottom of the image. The right nerve is on the left of each photomicrograph. (A) A young mouse (6 months of age) showing both optic nerves labeled from the globes to the optic chiasm. (B) An old mouse (10 months of age) showing relatively symmetric degeneration of both nerves. Degenerating nerves typically exhibit reduced label distally. (C) A second mouse at 10 months of age, showing asymmetric degeneration of it optic nerves. Only the left nerve is labeled. Bar = 0.5 mm.
Mentions: A cohort of 270 nerves from 135 D2 mice, aged between 6 and 22.5 months, was used in this analysis. Mice were euthanized and the nerves labeled with DiI as described in the methods. Figure 1 shows examples of labeling from young (Fig. 1A) and aged mice (Figs. 1B and 1C). Young mice typically showed robust DiI labeling extending to the optic chiasm. Mice that exhibited degeneration of their nerves typically fell into the general categories of those showing symmetric (Fig. 1B) or asymmetric degeneration (Fig. 1C). In this latter group, some mice exhibited one relatively healthy appearing nerve and nearly complete loss of staining in the other. Further evaluation of the asymmetry of degeneration in these mice is presented below.

Bottom Line: Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe.Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region.Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA. clschlamp@wisc.edu

ABSTRACT

Background: Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal ganglion cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the betaGeo reporter gene, to evaluate the time course of optic nerve degeneration and ganglion cell loss, respectively, in aging mice.

Results: Optic nerve degeneration, characterized by axon loss and gliosis is first apparent in mice between 8 and 9 months of age. Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe. Although nerve damage is typically bilateral, the progression of disease is asymmetric between the eyes of individual mice. Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region. Ganglion cell loss, as a function of the loss of betaGeo expression, is evident in some mice between 8 and 10 months of age and is prevalent in the majority of mice older than 10.5 months. Most eyes display a uniform loss of ganglion cells throughout the retina, but many younger mice exhibit focal loss of cells in sectors extending from the optic nerve head to the retinal periphery. Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal.

Conclusion: A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma.

Show MeSH
Related in: MedlinePlus