[Potential for neural regeneration in the adult mammalian retina].
[Potential for neural regeneration in the adult mammalian retina].
复制标题
[成年哺乳动物视网膜神经再生的潜力]。
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
S. Ooto
中科院分区：
文献类型：
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作者：
S. Ooto
目的
长期以来，人们一直认为成熟哺乳动物的视网膜不能再生。然而，我们在这里展示了成年哺乳动物的Müler神经胶质细胞可能是祖细胞，并产生新的视网膜神经元。
方法
将N-甲基-D-天冬氨酸(NMDA)注入成年大鼠(出生后6~7周)玻璃体内，造成神经毒性损伤。将溴脱氧尿苷(BrdU)注入玻璃体腔和腹膜腔，进行BrdU和细胞特异性标志物的免疫组织化学染色。为了测试外源性生长因子是否刺激细胞增殖，我们在NMDA处理后将维甲酸注入玻璃体腔。接下来，我们使用逆转录病毒表达系统在NMDA治疗的视网膜中表达MISEX表达的碱性螺旋-环-螺旋(BHLH)和同源盒基因。
结果
NMDA处理2天后，成年哺乳动物视网膜Müler神经胶质细胞因急性损伤而增殖。这些细胞获得了祖细胞样表型，其中一些迁移到外核层(ONL)。少数细胞表达双极或杆状光感受器特异性标记。维甲酸处理增加了双极细胞的发生。Math3或Neurd和Pax6的错误表达促进了向无长突细胞的分化。CRX和NeuD的共同表达促进了视杆的发生。
结论
这些发现表明，即使在成年哺乳动物的视网膜中，中毒损伤后也能再生视网膜神经元。我们可以通过外在因素或内在基因部分控制再生神经元的命运。
PURPOSE
It has long been believed that the retina of mature mammals is incapable of regeneration. However, here we show that Müller glia of adult mammals could be progenitor cells, and generate new retinal neurons.
METHODS
N-methyl-D-aspartate(NMDA) was injected into the vitreous chamber of adult rat (postnatal 6-7 weeks) eyes to induce neurotoxic injury. We injected bromo-deoxyuridine (BrdU) into the vitreous chamber and intraperitoneal space, and performed immunohistochemistry staining for BrdU and cell specific markers. To test whether exogenous growth factors stimulate proliferating cells, we injected retinoic acid into the vitreous chamber after NMDA treatment. We next misex-pressed basic helix-loop-helix (bHLH) and homeobox genes in NMDA-treated retinas using a retroviral expression system.
RESULTS
Müller glia of adult mammalian retinas proliferated in response to acute damage two days after NMDA treatment. These cells acquired a progenitor-like phenotype, and some of them migrated to the outer nuclear layer (ONL). A few of these cells expressed bipolar specific or rod photoreceptor specific markers. Retinoic acid treatment increased bipolar cell genesis. Misexpression of Math3 or NeuroD along with Pax6 promoted differentiation to amacrine cells. Co-expression of Crx and NeuroD promoted rod genesis.
CONCLUSIONS
These findings demonstrated that retinal neurons regenerated even in adult mammalian retinas after toxic injury. We could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes.