Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death.
Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death.
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DOI：
10.1371/journal.pone.0017659
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发表时间：
2011-03-29
期刊：
影响因子：
3.7
通讯作者：
Ksander BR
中科院分区：
文献类型：
--
作者：
Gregory MS;Hackett CG;Abernathy EF;Lee KS;Saff RR;Hohlbaum AM;Moody KS;Hobson MW;Jones A;Kolovou P;Karray S;Giani A;John SW;Chen DF;Marshak-Rothstein A;Ksander BR
青光眼是最常见的视神经病变，是全球失明的主要原因。视网膜神经节细胞（RGCs）的死亡发生在所有形式的青光眼中，并导致视力丧失，然而导致RGC丧失的分子机制尚不清楚。促凋亡分子Fas配体是一种跨膜蛋白，可被金属蛋白酶从细胞表面裂解，释放出具有拮抗活性的可溶性蛋白。先前的研究表明，FasL的组成性眼部表达维持了免疫特权并阻止了新生血管的发生。我们现在表明FasL也在视网膜神经毒性中起主要作用。重要的是，在TNFα引发的RGC死亡和自发性青光眼模型中，仅表达全长FasL的基因靶向小鼠表现出加速的RGC死亡。相比之下，FasL缺乏或可溶性FasL可保护RGCs免于细胞死亡。这些数据表明，膜结合FasL是青光眼的关键效应分子和潜在的治疗靶点。
Glaucoma, the most frequent optic neuropathy, is a leading cause of blindness worldwide. Death of retinal ganglion cells (RGCs) occurs in all forms of glaucoma and accounts for the loss of vision, however the molecular mechanisms that cause RGC loss remain unclear. The pro-apoptotic molecule, Fas ligand, is a transmembrane protein that can be cleaved from the cell surface by metalloproteinases to release a soluble protein with antagonistic activity. Previous studies documented that constitutive ocular expression of FasL maintained immune privilege and prevented neoangeogenesis. We now show that FasL also plays a major role in retinal neurotoxicity. Importantly, in both TNFα triggered RGC death and a spontaneous model of glaucoma, gene-targeted mice that express only full-length FasL exhibit accelerated RGC death. By contrast, FasL-deficiency, or administration of soluble FasL, protected RGCs from cell death. These data identify membrane-bound FasL as a critical effector molecule and potential therapeutic target in glaucoma.
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视网膜神经节细胞变性是拓扑的，但在DBA/2J小鼠中不是特异性细胞类型。
影响因子：
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