Samardzija Marijana, Wenzel Andreas, Aufenberg Svenja, Thiersch Markus, Remé Charlotte, Grimm Christian
Laboratory for Retinal Cell Biology, Department Ophthalmology, University Hospital, Frauenklinikstrasse 24, 8091 Zürich, Switzerland.
FASEB J. 2006 Nov;20(13):2411-3. doi: 10.1096/fj.06-5895fje. Epub 2006 Sep 11.
Retinal degeneration is a major cause of severe visual impairment or blindness. Understanding the underlying molecular mechanisms is a prerequisite to develop therapeutic approaches for human patients. We show in three mouse models that induced and inherited retinal degeneration induces LIF and CLC as members of the interleukin (IL)-6 family of proteins, activates proteins of the Jak-STAT signaling pathway, and up-regulates suppressors of cytokine signaling as a negative feedback loop. Inhibition of Jak2 leads to protection of photoreceptors in a model of induced but not in a model of inherited retinal degeneration. Differential activation of Akt suggests alternative pathways for cell death and/or survival in different models. Proteins induced during photoreceptor degeneration are not mainly expressed in photoreceptors but in cells of other retinal layers. This suggests a model in which photoreceptor injury is signaled to cells of the inner retina, which in turn initiate a response either to support viability or accelerate death of injured cells.
视网膜变性是严重视力损害或失明的主要原因。了解其潜在的分子机制是为人类患者开发治疗方法的先决条件。我们在三种小鼠模型中表明，诱导性和遗传性视网膜变性会诱导白血病抑制因子（LIF）和睫状神经营养因子（CLC）作为白细胞介素（IL）-6蛋白家族的成员，激活Jak-STAT信号通路的蛋白，并上调细胞因子信号转导抑制因子作为负反馈环。在诱导性视网膜变性模型中，抑制Jak2可导致光感受器得到保护，但在遗传性视网膜变性模型中则不然。Akt的差异激活表明在不同模型中细胞死亡和/或存活存在替代途径。光感受器变性过程中诱导产生的蛋白质并非主要在光感受器中表达，而是在视网膜其他层的细胞中表达。这提示了一种模型，即光感受器损伤会向内视网膜细胞发出信号，进而引发一种反应，要么支持受损细胞的存活，要么加速其死亡。
