The Bcl-2 family member BIM has multiple glaucoma-relevant functions in DBA/2J mice.
The Bcl-2 family member BIM has multiple glaucoma-relevant functions in DBA/2J mice.
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DOI：
10.1038/srep00530
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发表时间：
2012
影响因子：
4.6
通讯作者：
Libby, Richard T.
中科院分区：
文献类型：
--
作者：
Harder, Jeffrey M.;Fernandes, Kimberly A.;Libby, Richard T.
轴突损伤通过BAX依赖性过程诱导视网膜神经节细胞（RGC）死亡。已知促凋亡Bcl-2家族成员BIM诱导BAX活化。视神经损伤后，RGC中BIM的表达增加，其诱导依赖于JUN。部分和完全Bim缺乏延迟机械性视神经损伤后RGC的死亡。然而，在青光眼的小鼠模型中，DBA/2 J小鼠，Bim缺乏并不能阻止具有严重视神经变性的眼睛中的RGC死亡。在DBA/2 J小鼠的一个亚组中，Bim缺乏改变了疾病进展，导致神经损伤不太严重。Bim缺陷小鼠表现出改变视神经乳头形态和显着减少眼内压升高。因此，Bim缺陷DBA/2 J小鼠轴突变性的减少可能不是由Bim在RGCs中的直接作用引起的。这些数据表明BIM在青光眼病理生理学中具有多种作用，可能通过多种机制影响青光眼易感性。
Axonal insult induces retinal ganglion cell (RGC) death through a BAX-dependent process. The pro-apoptotic Bcl-2 family member BIM is known to induce BAX activation. BIM expression increased in RGCs after axonal injury and its induction was dependent on JUN. Partial and complete Bim deficiency delayed RGC death after mechanical optic nerve injury. However, in a mouse model of glaucoma, DBA/2J mice, Bim deficiency did not prevent RGC death in eyes with severe optic nerve degeneration. In a subset of DBA/2J mice, Bim deficiency altered disease progression resulting in less severe nerve damage. Bim deficient mice exhibited altered optic nerve head morphology and significantly lessened intraocular pressure elevation. Thus, a decrease in axonal degeneration in Bim deficient DBA/2J mice may not be caused by a direct role of Bim in RGCs. These data suggest that BIM has multiple roles in glaucoma pathophysiology, potentially affecting susceptibility to glaucoma through several mechanisms.
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影响因子：
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