Early microglia activation in a mouse model of chronic glaucoma.
Early microglia activation in a mouse model of chronic glaucoma.
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DOI：
10.1002/cne.22516
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发表时间：
2011-03-01
影响因子：
2.5
通讯作者：
Vetter, Monica L.
中科院分区：
文献类型：
--
作者：
Bosco, Alejandra;Steele, Michael R.;Vetter, Monica L.
小胶质细胞活化和分布的变化与CNS中的神经元衰退相关，特别是在病理条件下。活化的小胶质细胞聚集在人类青光眼轴突变性的起始部位，然而，它们在其病理生理学中的作用仍然没有得到解决。开始时，尚不清楚小胶质细胞活化是否先于视网膜神经节细胞（RGC）神经变性或为视网膜神经节细胞（RGC）神经变性的晚期后果。在这里，我们在DBA/2 J（D2）小鼠中解决了这一关键因素，这是一种已建立的慢性遗传性青光眼模型，使用不受青光眼影响的同类亚株DBA/2 J Gpnmb+/SjJ（D2 G）作为对照。我们分析了小胶质细胞在视网膜中的变化的空间分布和时程，以及在近端视神经之前和整个年龄时，神经变性的报告。仅在D2小鼠中，我们检测到早期小胶质细胞聚集在内部中央视网膜和无髓鞘视神经区域，小胶质细胞活化在3个月大时达到峰值。在5至8月龄之间，活化的小胶质细胞持续存在并集中在视盘中，但也定位于视网膜周边。总的来说，我们的研究结果表明，小胶质细胞激活是D2青光眼视网膜和视神经的早期改变，可能有助于疾病的发作或进展。最终，检测小胶质细胞活化可能在早期疾病诊断中具有价值，而调节小胶质细胞反应可能改变疾病进展。
Changes in microglial cell activation and distribution are associated with neuronal decline in the CNS, particularly under pathological conditions. Activated microglia converge on the initial site of axonal degeneration in human glaucoma, yet, their part in its pathophysiology remains unresolved. To begin with, it is unknown whether microglia activation precedes or is a late consequence of retinal ganglion cell (RGC) neurodegeneration. Here, we address this critical element in DBA/2J (D2) mice, an established model of chronic inherited glaucoma, using as a control the congenic substrain DBA/2J Gpnmb+/SjJ (D2G), which is not affected by glaucoma. We analyzed the spatial distribution and timecourse of microglial changes in the retina, as well as within the proximal optic nerve prior to and throughout ages when neurodegeneration has been reported. Exclusively in D2 mice, we detected early microglia clustering in the inner central retina and unmyelinated optic nerve regions, with microglia activation peaking by 3 months of age. Between 5 and 8 months of age, activated microglia persisted and concentrated in the optic disc, but also localized to the retinal periphery. Collectively, our findings suggest microglia activation is an early alteration in the retina and optic nerve in D2 glaucoma, potentially contributing to disease onset or progression. Ultimately, detection of microglial activation may have value in early disease diagnosis, while modulation of microglial responses may alter disease progression.
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影响因子：
3.3
作者：
Douglas, R. M.;Lai, J. C. K.;Haddad, G. G.
通讯作者：
Haddad, G. G.
DOI：
10.1073/pnas.0913141107
发表时间：
2010-03-16
影响因子：
11.1
作者：
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通讯作者：
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作者：
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通讯作者：
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2.5
作者：
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通讯作者：
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影响因子：
30.8
作者：
Anderson, MG;Smith, RS;John, SWM
通讯作者：
John, SWM