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首页> 外文期刊>The European Journal of Neuroscience >The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model.
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The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model.

机译：WldS基因可延缓大鼠青光眼模型中的轴突变性，但不会延缓其退化。

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摘要

Glaucoma is a leading cause of blindness caused by progressive degeneration of retinal ganglion cells (RGCs) and their axons. The pathogenesis of glaucoma remains incompletely understood, but optic nerve (ON) axonal injury appears to be an important trigger of RGC axonal and cell body degeneration. Rat models are widely used in glaucoma research to explore pathogenic mechanisms and to test novel neuroprotective approaches. Here we investigated the mechanism of axon loss in glaucoma, studying axon degeneration in slow Wallerian degeneration (Wld(S)) rats after increasing intraocular pressure. Wld(S) delays degeneration of experimentally transected axons for several weeks, so it can provide genetic evidence for Wallerian-like degeneration in disease. As apoptosis is unaffected, Wld(S) also provides information on whether cell death results from axon degeneration or arises independently, an important question yet to be resolved in glaucoma. Having confirmed expression of Wld(S) protein, we found that Wld(S) delayed ON axonal degeneration in experimental rat glaucoma for at least 2 weeks, especially in proximal ON where wild-type axons are most severely affected. The duration of axonal protection is similar to that after ON transection and crush, suggesting that axonal degeneration in glaucoma follows a Wallerian-like mechanism. Axonal degeneration must be prevented for RGCs to remain functional, so pharmacologically mimicking and enhancing the protective mechanism of Wld(S) could offer an important route towards therapy. However, Wld(S) did not protect RGC bodies in glaucoma or after ON lesion, suggesting that combination treatments protecting both axons and cell bodies offer the best therapeutic prospects.
机译：青光眼是由视网膜神经节细胞（RGCs）及其轴突进行性变性引起的失明的主要原因。青光眼的发病机理尚不完全清楚，但视神经（ON）轴突损伤似乎是RGC轴突和细胞体变性的重要诱因。大鼠模型广泛用于青光眼研究，以探究其致病机制并测试新型的神经保护方法。在这里，我们研究了青光眼轴突丢失的机制，研究了眼压升高后缓慢的沃勒变性（Wld（S））大鼠的轴突变性。 Wld（S）将实验性横断轴突的变性延迟了数周，因此可以为疾病中类似Wallerian的变性提供遗传证据。由于凋亡不受影响，Wld（S）还提供有关细胞死亡是由轴突变性导致还是独立发生的信息，这是青光眼中尚未解决的重要问题。确认Wld（S）蛋白的表达后，我们发现Wld（S）将实验大鼠青光眼的ON轴突变性延迟至少2周，尤其是在野生型轴突受到最严重影响的近端ON中。轴突保护的持续时间类似于ON横断和挤压后的持续时间，表明青光眼中的轴突变性遵循Wallerian-like机制。必须防止轴突变性以使RGC保持功能，因此在药理学上模仿和增强Wld（S）的保护机制可能为治疗提供重要途径。但是，Wld（S）不能保护青光眼或ON病变后的RGC体，这表明同时保护轴突和细胞体的联合治疗可提供最佳的治疗前景。

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