Progressive damage along the optic nerve following induction of crush injury or rodent anterior ischemic optic neuropathy in transgenic mice.

Abstract

PURPOSE:

To characterize the histological changes that occur in response to induction of ischemic or mechanical optic nerve damage in transgenic mice.

METHODS:

Either optic nerve crush injury or rodent anterior ischemic optic neuropathy (rAION) were induced in the right eye of mice transgenic for the Thy1 gene promoter expressing cyan fluorescent protein (CFP; n=40) and mice transgenic for the cyclic nucleotide phosphodiesterase (CNPase) gene promoter expressing green fluorescent protein (GFP; n=40). The left eye served as a control. The mice were euthanized at different times after injury. Eyes were enucleated, and the brain together with the optic nerves was completely dissected. Cryopreserved sections of both optic nerves were analyzed by fluorescence microscopy. In addition, flat-mounted retinas from the Thy1-CFP mice were analyzed for retinal ganglion cell (RGC) loss.

RESULTS:

Axonal loss was detected in the right eye of the Thy1-CFP mice, and demyelination was detected in the CNPase-GFP mice. Both processes occurred simultaneously in the two models of injury. The damage proceeded retrogradely and, in the crush-injury group, crossed the chiasm within 4 days. At 21 days after injury, RGC loss measured 70% in the crush-injury group and 25% in the rAION group.

CONCLUSIONS:

Axonal injury and demyelination along the optic nerves occur simultaneously in transgenic mice exposed to ischemic or crush injury. The degree of RGC loss reflects the severity of the injury. Loss of oligodendrocytes and myelin apparently leads to axonal loss. Transgenic mice offer a promising model for exploring the damage caused by optic nerve injury. Use of fluorescence labeling makes it possible to better understand the underlying pathophysiology, which can help researchers formulate neuroprotective agents.

• Authors: O Dratviman-Storobinsky, M Hasanreisoglu, D Offen, Y Barhum, D Weinberger, N Goldenberg-Cohen
• Journal: Molecular vision (Mol Vis) Vol. 14 Pg. 2171-9 ( 2008) ISSN: 1090-0535 [Electronic] United States
• PMID: 19052651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyan Fluorescent Protein
• Thy-1 Antigens
• Green Fluorescent Proteins
• 2',3'-Cyclic-Nucleotide Phosphodiesterases

Topics

• 2',3'-Cyclic-Nucleotide Phosphodiesterases (metabolism)
• Animals
• Apoptosis
• Axons (pathology)
• Disease Models, Animal
• Green Fluorescent Proteins (metabolism)
• In Situ Nick-End Labeling
• Mice
• Mice, Transgenic
• Oligodendroglia (pathology)
• Optic Chiasm (pathology)
• Optic Nerve (metabolism, pathology)
• Optic Nerve Injuries (chemically induced, metabolism, pathology)
• Optic Neuropathy, Ischemic (pathology)
• Retinal Ganglion Cells (metabolism, pathology)
• Thy-1 Antigens (metabolism)