Abreu Carla Andreia, De Lima Silmara Veline, Mendonça Henrique Rocha, Goulart Camila de Oliveira, Martinez Ana Maria Blanco
Department of Pathology, Medical College, HUCFF, UFRJ, Rio de Janeiro, Brazil.
Laboratory of Neurodegeneration and Repair, Medical College, HUCFF, UFRJ, Rio de Janeiro, Brazil.
Histol Histopathol. 2017 Mar;32(3):253-262. doi: 10.14670/HH-11-788. Epub 2016 Jun 3.
A trauma to the mature central nervous system (CNS) often leads to persistent deficits, due to the inability of axons to regenerate after being injured. Increasing evidence suggests that pro-inflammatory and pro-apoptotic genes can present a major obstacle to promoting neuroprotection of retinal ganglion cells and consequently succeed in axonal regeneration. This study evaluated the effect of the absence of galectin-3 (Gal-3) on retinal ganglion cells (RGC) survival and axonal regeneration/degeneration after optic nerve crush injury. Two weeks after crush there was a 2.6 fold increase in the rate of cell survival in Gal-3-/- mice (1283±79.15) compared to WT animals (495.4±53.96). However, no regeneration was observed in the Gal-3-/- mice two weeks after lesion. Furthermore, axonal degeneration presented a particular pattern on those mice; Electron Microscopy (EM) analysis showed incomplete axon degeneration while the WT mice presented an advanced stage of degeneration. This suggests that the removal of the nerve fibers in the Gal 3-/- mice could be deficient and this would cause a delay in the process of Wallerian degeneration once there is a decrease in the number of macrophages/microglia in the nerve. This study demonstrates how the absence of Gal-3 can affect RGC survival and optic nerve regeneration/degeneration after lesion. Our results suggest that the absence of Gal-3 plays an important role in the survival of RGC and thus can be a potential target for therapeutic intervention in RGC neuroprotection.
成熟的中枢神经系统（CNS）受到创伤后，常常会导致永久性缺陷，这是因为轴突在受伤后无法再生。越来越多的证据表明，促炎基因和促凋亡基因可能是促进视网膜神经节细胞神经保护从而实现轴突再生的主要障碍。本研究评估了缺乏半乳糖凝集素-3（Gal-3）对视神经挤压伤后视网膜神经节细胞（RGC）存活以及轴突再生/退变的影响。挤压伤两周后，Gal-3基因敲除小鼠（1283±79.15）的细胞存活率相比野生型动物（495.4±53.96）提高了2.6倍。然而，损伤两周后，Gal-3基因敲除小鼠未观察到再生现象。此外，这些小鼠的轴突退变呈现出一种特殊模式；电子显微镜（EM）分析显示轴突退变不完全，而野生型小鼠则处于退变的晚期阶段。这表明Gal 3基因敲除小鼠的神经纤维清除可能存在缺陷，一旦神经中巨噬细胞/小胶质细胞数量减少，这将导致华勒氏变性过程延迟。本研究证明了Gal-3的缺失如何影响损伤后RGC的存活以及视神经的再生/退变。我们的结果表明，Gal-3的缺失在RGC存活中起重要作用，因此可能成为RGC神经保护治疗干预的潜在靶点。
