Recently, regeneration of CNS tracts has been partially accomplished by strategies of intrinsic neuronal growth stimulation. However, restoration of function is dependent on proper myelination of regenerating axons. Previous work from our group (Goulart et al., 2018) has shown an increase in oligodendrocyte staining in the regenerating optic nerve, 2 weeks after crush, in animals that were submitted to conditional deletion of pten gene in retinal ganglion cells and intravitreal injection of zymosan + cAMP. Thus, in the present study we aimed to investigate the maturation of the oligodendroglial lineage and myelination during the regeneration of the optic nerve under the same conditions of our previous work. We showed that the combined treatment promoted an increase of myelinated fibers within the optic nerve, 12 weeks after lesion, as well as an increase in Sox10 positive cells. Early-OPCs, positive to A2B5, were also increased at 12 weeks, whereas O4 positive, late-OPCs, were increased from 2 until 12 weeks after crush. At 12 weeks after crush, the optic nerve of Regenerating group presented more CC1 positive oligodendrocytes and increased MRF positive myelinating oligodendrocytes, culminating in CTB traced regenerating axons superimposed to MBP staining, suggestive of myelination. Thus, our work showed that conditional deletion of pten gene in retinal ganglion cells and intravitreal inflammatory stimuli + cAMP stimulate full maturation of the olidodendroglial lineage, from OPC proliferation and differentiation to myelination of regenerating CNS axons.

最近，CNS 束的再生已部分通过内在神经元生长刺激策略实现。然而，功能的恢复取决于再生轴突的适当髓鞘形成。我们小组之前的工作（Goulart 等人，2018 年）表明，在被条件性删除pten 的动物中，在挤压后 2 周，再生视神经中少突胶质细胞染色增加视网膜神经节细胞中的基因和玻璃体内注射酵母聚糖 + cAMP。因此，在本研究中，我们旨在研究在与我们之前工作相同的条件下视神经再生过程中少突胶质细胞谱系的成熟和髓鞘形成。我们表明，联合治疗促进了视神经内有髓纤维的增加，损伤后 12 周，以及 Sox10 阳性细胞的增加。对 A2B5 呈阳性的早期 OPCs 也在 12 周时增加，而 O4 阳性的晚期 OPCs 在挤压后 2 至 12 周期间增加。挤压后12周，再生组视神经CC1阳性少突胶质细胞增多，MRF阳性髓鞘少突胶质细胞增多，最终CTB示踪再生轴突叠加MBP染色，提示髓鞘形成。因此，我们的工作表明，条件删除视网膜神经节细胞中的pten基因和玻璃体内炎症刺激物 + cAMP 刺激少突胶质细胞谱系的完全成熟，从 OPC 增殖和分化到再生中枢神经系统轴突的髓鞘形成。