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

被引：484

作者：

Howell, Gareth R. ^{[1
]}

Libby, Richard T. ^{[1
]}

Jakobs, Tatjana C. ^{[2
]}

Smith, Richard S. ^{[1
,3
]}

Phalan, F. Campbell ^{[1
,3
]}

Barter, Joseph W. ^{[1
,3
]}

Barbay, Jessica M. ^{[1
]}

Marchant, Jeffrey K. ^{[4
]}

Mahesh, Nagaraju ^{[5
]}

Porciatti, Vittorio ^{[5
]}

Whitmore, Alan V. ^{[1
]}

Masland, Richard H. ^{[2
]}

John, Simon W. M. ^{[1
,3
,6
]}

机构：

[1] Jackson Lab, Bar Harbor, ME 04609 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA

[3] Howard Hughes Med Inst, Bar Harbor, ME 04609 USA

[4] Tufts Univ, Dept Anat & Cell Biol, Boston, MA 02111 USA

[5] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA

[6] Tufts Univ Med, Dept Ophthalmol, Boston, MA 02111 USA

来源：

JOURNAL OF CELL BIOLOGY | 2007年 / 179卷 / 07期

关键词：

D O I：

10.1083/jcb.200706181

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1523 / 1537

页数：15

共 81 条

[51] Tumor necrosis factor-α mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma [J].