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

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

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Retinal Ganglion Cells
Optic Nerve
Glaucoma
Axons
Inbred DBA Mouse
Astrocytes
Electroretinography
Retina
Alleles

ASJC Scopus subject areas

  • Cell Biology

Cite this

Howell, G. R., Libby, R. T., Jakobs, T. C., Smith, R. S., Phalan, F. C., Barter, J. W., ... 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

Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. / Howell, Gareth R.; Libby, Richard T.; Jakobs, Tatjana C.; Smith, Richard S.; Phalan, F. Campbell; Barter, Joseph W.; Barbay, Jessica M.; Marchant, Jeffrey K.; Mahesh, Nagaraju; Porciatti, Vittorio; Whitmore, Alan V.; Masland, Richard H.; John, Simon W M.

In: Journal of Cell Biology, Vol. 179, No. 7, 31.12.2007, p. 1523-1537.

Research output: Contribution to journalArticle

Howell, GR, Libby, RT, Jakobs, TC, Smith, RS, Phalan, FC, Barter, JW, Barbay, JM, Marchant, JK, Mahesh, N, Porciatti, V, Whitmore, AV, Masland, RH & John, SWM 2007, 'Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma', Journal of Cell Biology, vol. 179, no. 7, pp. 1523-1537. https://doi.org/10.1083/jcb.200706181
Howell GR, Libby RT, Jakobs TC, Smith RS, Phalan FC, Barter JW et al. Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. Journal of Cell Biology. 2007 Dec 31;179(7):1523-1537. https://doi.org/10.1083/jcb.200706181
Howell, Gareth R. ; Libby, Richard T. ; Jakobs, Tatjana C. ; Smith, Richard S. ; Phalan, F. Campbell ; Barter, Joseph W. ; Barbay, Jessica M. ; Marchant, Jeffrey K. ; Mahesh, Nagaraju ; Porciatti, Vittorio ; Whitmore, Alan V. ; Masland, Richard H. ; John, Simon W M. / Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. In: Journal of Cell Biology. 2007 ; Vol. 179, No. 7. pp. 1523-1537.
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