期刊
JOURNAL OF CELL BIOLOGY
卷 179, 期 7, 页码 1523-1537出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200706181
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资金
- NCI NIH HHS [P30 CA034196, CA34196] Funding Source: Medline
- NEI NIH HHS [R03 EY016322, F32 EY014515, P30-EY14801, F32EY014515, R01 EY017169, R03 EY016322-03, EY017169, P30 EY014801] Funding Source: Medline
Here, we use a mouse model (DBA/2J) to re address 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-defficient 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 Wld(s) 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.
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