Hauk Thomas G, Müller Adrienne, Lee Jieun, Schwendener Reto, Fischer Dietmar
Department of Experimental Neurology, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany.
Exp Neurol. 2008 Feb;209(2):469-82. doi: 10.1016/j.expneurol.2007.09.020. Epub 2007 Sep 29.
Retinal ganglion cells (RGCs) cannot regenerate their axons after injury and undergo apoptosis soon after an intraorbital injury of the optic nerve. However, RGCs reactivate their axonal growth program when inflammatory reactions occur in the eye, which enables them to survive axotomy and to regenerate lengthy axons into the lesioned optic nerve. Lens injury (LI) and zymosan injections can induce these beneficial processes and provoke also a strong accumulation of activated macrophages in the vitreous body. It has recently been suggested that macrophage-derived oncomodulin is the principal mediator of this phenomenon. We show here that oncomodulin is not significantly expressed in primary macrophages and that the intraocular levels of this protein do not increase after LI or zymosan treatment. Furthermore, greatly reducing the invasion of macrophages into the inner eye does not diminish the neuroprotective effects of LI, but rather increases axon regeneration into the optic nerve. Axon regeneration is correlated with the activation of retinal astrocytes and Müller cells. Our data suggest that intraocular inflammation mediates its main beneficial effects through factors other than oncomodulin and that the underlying mechanism might be independent of the presence of activated macrophages.
视网膜神经节细胞（RGCs）在损伤后无法再生其轴突，并且在眶内视神经损伤后不久就会发生凋亡。然而，当眼部发生炎症反应时，RGCs会重新激活其轴突生长程序，这使它们能够在轴突切断后存活，并将长轴突再生到受损的视神经中。晶状体损伤（LI）和酵母聚糖注射可以诱导这些有益的过程，并且还会促使玻璃体中活化巨噬细胞大量聚集。最近有人提出，巨噬细胞衍生的癌胚钙结合蛋白是这一现象的主要介导因子。我们在此表明，癌胚钙结合蛋白在原代巨噬细胞中没有明显表达，并且在LI或酵母聚糖处理后，该蛋白的眼内水平并未升高。此外，大幅减少巨噬细胞向内眼的浸润并不会削弱LI的神经保护作用，反而会增加轴突向视神经的再生。轴突再生与视网膜星形胶质细胞和米勒细胞的激活相关。我们的数据表明，眼内炎症通过癌胚钙结合蛋白以外的因素介导其主要有益作用，并且潜在机制可能独立于活化巨噬细胞的存在。
