Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma

Gareth R. Howell, Richard T. Libby, Tatjana C. Jakobs, Richard S. Smith, F. Campbell Phalan, Joseph W. Barter, Jessica M. Barbay, Jeffrey K. Marchant, Nagaraju Mahesh, Vittorio Porciatti, Alan V. Whitmore, Richard H. Masland, Simon W.M. John

Research output: Contribution to journalArticle

345 Scopus citations

Abstract

Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wlds allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.

Original languageEnglish (US)
Pages (from-to)1523-1537
Number of pages15
JournalJournal of Cell Biology
Volume179
Issue number7
DOIs
StatePublished - Dec 31 2007

ASJC Scopus subject areas

  • Cell Biology

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    Howell, G. R., Libby, R. T., Jakobs, T. C., Smith, R. S., Phalan, F. C., Barter, J. W., Barbay, J. M., Marchant, J. K., Mahesh, N., Porciatti, V., Whitmore, A. V., Masland, R. H., & John, S. W. M. (2007). Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. Journal of Cell Biology, 179(7), 1523-1537. https://doi.org/10.1083/jcb.200706181