High-dose radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma

被引:102
作者
Anderson, MG
Libby, RT
Gould, DB
Smith, RS
John, SWM
机构
[1] Jackson Lab, Bar Harbor, ME 04609 USA
[2] Howard Hughes Med Inst, Bar Harbor, ME 04609 USA
[3] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA
关键词
neuroprotection; retinal ganlgion cell; mouse model;
D O I
10.1073/pnas.0407357102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Here, we show that high-dose gamma-irradiation accompanied with syngeneic bone marrow transfer can confer complete protection against glaucoma in a mouse model. Because bone marrow genotype was unaltered by this procedure, it was not the causative agent. The neuroprotection is robust and highly reproducible. Glaucoma-prone DBA/2J mice received a single treatment at 5-8 weeks of age and were protected from glaucomatous retinal ganglion cell degeneration out to 14 months of age (oldest assessed). By 12-14 months, retinal ganglion cell degeneration is usually very severe and essentially complete in the majority of untreated DBA/2J mice. To assess reproducibility, three groups of mice were treated at different times, and the results were essentially the same each time. Considering all experiments, the vast majority of treated mice had no detectable glaucomatous neurodegeneration. A beneficial effect of treatment including high-dose radiation is unprecedented, and we are not aware of any other neuroprotective effects this substantial. Because of the robust protective effect, this treatment offers another tool for studying mechanisms of neuroprotection.
引用
收藏
页码:4566 / 4571
页数:6
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