Optic Nerve Regeneration Induced In Adult Mice

NEW YORK (Reuters Health) - The ability to regenerate damaged optic nerves is closer to reality with increased understanding of underlying mechanisms, investigators report in the March issue of the Journal of Cell Science.

Working with murine retinal ganglion cells, Dr. Dong Feng Chen of Harvard Medical School, Boston, and her colleagues found that under normal conditions, these cells can elongate only until embryonic day 18.

"We found that the anti-apoptotic gene Bcl-2 is expressed in neurons in the embryonic stage, correlating with the period when they are actively growing, then is 'turned off' as neurons lose the ability to grow or regenerate," Dr. Chen told Reuters Health.

To further explore the implications of these findings, Dr. Chen's group generated Bcl-2tg mice in which Bcl-2 is overexpressed.

Following crush injury to the optic nerve in neonatal mice, the nerve fibers in wild-type animals exhibited no regenerative response. Those in Bcl-2tg mice continued to regrow up until postnatal day 4 at rates similar to those observed during embryonic growth. By day 4, axons had traveled along optic tract pathways and reached their midbrain targets.

By postnatal day 5, however, axon growth had terminated, suggesting an inhibitory mechanism in the mature central nervous system environment, Dr. Chen said.

They theorized that maturation of astrocytes in the midbrain that enables the formation of glial scarring may put the brake on optic nerve growth. To test this, they generated another strain of mice lacking expression of vimentin, which is expressed in immature astrocytes, and glial fibrillary acid protein (GFAP), a marker of mature astrocytes. These mice were incapable of glial scarring.

Only in animals constitutively expressing Bcl-2 and lacking vimentin and GFAP did severed axons continue to regenerate and extend within the brain for up to 2 months.

"Suppression of glial scarring after injury," the authors suggest, "is sufficient to allow rapid regeneration of the severed optic nerve over long distances and target innervation in mature Bcl-2tg mice."

Dr. Chen added that the next step will be investigation of visual evoked potentials in the mice to ascertain that regenerated axon growth leads to restored vision.

Source: J Cell Sci 2005. [ Google search on this article ]

MeSH Headings: Nerve Regeneration : Genes, bcl-2

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