Retinal ganglion cell (RGC) degeneration, leading to irreversible blindness in chronic optic neuropathies, commonly begins with dendritic shrinkage followed by axon degeneration. Although limited axon regeneration in the optic nerve is possible with a genetic deletion of PTEN/SOCS3 after optic nerve injury, the roles of PTEN/SOCS3 on dendritic preservation and regeneration remain unclear. This study investigated the effect of PTEN/SOCS3 genetic deletion on the structural integrity of RGC dendrites and axons in the retina following optic nerve crush. Using time-lapse, in vivo confocal scanning laser ophthalmoscopy to serially image dendritic and axonal arborizations of RGCs over six months after injury, RGC dendrites and axons were only preserved in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice, and axons in the retina regenerated at a rate of 21.1 μm/day and 15.5 μm/day, respectively. By contrast, dendritic complexity significantly decreased in Thy-1-YFP-SOCS3-/- and control mice at a rate of 7.0 %/day and 7.1 %/day, respectively, and no axon regeneration in the retina was observed. RGC survival probability was higher in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice compared with Thy-1-YFP-SOCS3-/- and control mice. The differential responses between the transgenic mice demonstrate that although a genetic deletion of PTEN, SOCS3, or PTEN/SOCS3 allows partial axon regeneration in the optic nerve after optic nerve crush, a deletion of PTEN, but not SOCS3, ameliorates RGC dendritic shrinkage. This shows that the signaling pathways involved in promoting axon regeneration do not equally contribute to the preservation of dendrites, which is crucial to the translational application of neuroregenerative therapies for visual restoration.

中文翻译：

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PTEN / SOCS3缺失对视神经损伤后视网膜神经节细胞树突收缩的改善作用。

视网膜神经节细胞（RGC）变性导致慢性视神经病变中不可逆转的失明，通常始于树突收缩，然后是轴突变性。尽管视神经损伤后通过基因缺失PTEN / SOCS3可能导致视神经轴突再生受限，但PTEN / SOCS3在树突状细胞保存和再生中的作用仍不清楚。这项研究调查了PTEN / SOCS3基因缺失对视神经挤压后视网膜RGC树突和轴突结构完整性的影响。使用延时共聚焦扫描激光眼底镜在损伤后六个月内连续成像RGC的树突和轴突乔化，RGC树突和轴突仅保存在Thy-1-YFP / PTEN-/-和Thy-1-YFP中/ PTEN-/-SOCS3-/-小鼠，视网膜中的轴突和轴突分别以21.1μm/天和15.5μm/天的速度再生。相比之下，在Thy-1-YFP-SOCS3-/-和对照小鼠中，树突状复杂性分别以7.0％/天和7.1％/天的速率显着降低，并且未观察到视网膜中的轴突再生。与Thy-1-YFP-SOCS3-/-和对照小鼠相比，Thy-1-YFP / PTEN-/-和Thy-1-YFP / PTEN-/-SOCS3-/-小鼠的RGC存活概率更高。转基因小鼠之间的差异反应表明，尽管PTEN，SOCS3或PTEN / SOCS3的基因缺失可导致视神经压迫后视神经部分轴突再生，但PTEN的缺失而非SOCS3的缺失可改善RGC树突收缩。这表明参与促进轴突再生的信号通路并不能同等地促进树突的保存，