The Bcl-2 family member BIM has multiple glaucoma-relevant functions in DBA/2J mice

被引：37

作者：

Harder, Jeffrey M. ^{[1
,2
]}

Fernandes, Kimberly A. ^{[1
,3
]}

Libby, Richard T. ^{[1
,4
,5
]}

机构：

[1] Univ Rochester, Med Ctr, Flaum Eye Inst, Rochester, NY 14642 USA

[2] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA

[3] Univ Rochester, Med Ctr, Interdept Grad Program Neurosci, Rochester, NY 14642 USA

[4] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA

[5] Univ Rochester, Med Ctr, Ctr Visual Sci, Rochester, NY 14642 USA

来源：

SCIENTIFIC REPORTS | 2012年 / 2卷

关键词：

RETINAL GANGLION-CELLS; OPEN-ANGLE GLAUCOMA; TO-DISC RATIO; MOUSE MODEL; INTRAOCULAR-PRESSURE; NEURONAL DEATH; EXPRESSION; BAX; DEGENERATION; ACTIVATION;

D O I：

10.1038/srep00530

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：

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.

引用

页数：7