Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration.
Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration.
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DOI：
10.1523/jneurosci.5956-09.2010
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发表时间：
2010-04-21
期刊：
影响因子：
--
通讯作者：
Horner PJ
中科院分区：
文献类型：
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作者：
Baltan S;Inman DM;Danilov CA;Morrison RS;Calkins DJ;Horner PJ
我们在青光眼的DBA/2 J小鼠模型中测试了青光眼破坏视神经中的电生理传导特性和轴突功能作为眼内压（IOP）水平和年龄的函数的假设。作为增加IOP水平的函数，在6个月龄时沿沿着轴突诱发的电信号的幅度和积分显著降低。在年轻时，IOP升高与代谢挑战的脆弱性增加直接相关。视神经生理功能的变化随着年龄的增长而加重，导致整个纤维群体中的复合动作电位丧失，这些纤维是小的、传导缓慢的轴突。这种损失伴随着小纤维轴突计数的损失和代谢储备的下降，证明了小鼠视神经中的IOP依赖性ATP减少。这些数据揭示了青光眼病理学的一种新的潜在机制，即IOP升高和代谢能力下降导致轴突易感性，最终导致功能障碍和丧失。
We tested the hypothesis that glaucoma disrupts electrophysiological conduction properties and axon function in optic nerve as a function of intraocular pressure (IOP) levels and age in the DBA/2J mouse model of glaucoma. The amplitude and the integral of electrical signals evoked along the axons decreased considerably by 6 months of age as a function of increasing IOP levels. At young ages, raised IOP was directly associated with increased vulnerability to metabolic challenge. Changes in the physiological function of the optic nerves were accentuated with aging, leading to loss of compound action potential in an entire population of fibers—small, slow conducting axons. This loss was accompanied with loss of small fiber axon counts and declining metabolic reserve by demonstrating IOP-dependent ATP decrease in mouse optic nerves. These data shed light on a novel potential mechanism of glaucoma pathology whereby increased IOP and declining metabolic capacity lead to axon liability and eventually dysfunction and loss.