Li Yan, Zhou Guo-Min
Department of Anatomy, Histology and Embryology, School of Basic Medical Science, Fudan University, Shanghai, China.
Neuroreport. 2015 Aug 19;26(12):712-7. doi: 10.1097/WNR.0000000000000414.
The mammalian retina has the potential to regenerate rod cells, bipolar cells, and amacrine cells in vivo to repair damaged nervous tissue through the Müller glial cell (MGC)-mediated response. Both horizontal cell (HC) and amacrine cell are interneurons in the inner nuclear layer (INL) and are generated under the control of some common transcription factors during retinal development. However, to date, the ability of HC regeneration in vivo in mammals remains unclear. Here, ouabain (a Na/K-ATPase inhibitor) was injected into rat eyes to induce an obvious cell loss in the INL. The proliferation, dedifferentiation of MGC and production of new neurons after ouabain injection were examined by BrdU incorporation and immunohistochemistry. Our results showed that 2 days after ouabain treatment, MGCs incorporated BrdU and upregulated the expression of Nestin, which is a marker for retinal progenitor cells. Several weeks after ouabain injection, the BrdU-positive cells in the outer border of the INL expressed Prox1 and Calbindin D-28k, which are specific markers for HC. Taken together, these results suggest that the mammalian retina can regenerate new type of interneurons (HC) in vivo, which advances our understanding of mammalian retinal regeneration after damage.
哺乳动物的视网膜具有在体内再生视杆细胞、双极细胞和无长突细胞的潜力，可通过穆勒胶质细胞（MGC）介导的反应修复受损的神经组织。水平细胞（HC）和无长突细胞均为内核层（INL）中的中间神经元，且在视网膜发育过程中受一些共同转录因子的控制而生成。然而，迄今为止，哺乳动物体内HC再生的能力仍不明确。在此，将哇巴因（一种钠钾ATP酶抑制剂）注入大鼠眼内，以诱导INL中出现明显的细胞丢失。通过BrdU掺入法和免疫组织化学法检测哇巴因注射后MGC的增殖、去分化以及新神经元的产生。我们的结果显示，哇巴因处理2天后，MGC掺入BrdU并上调视网膜祖细胞标志物巢蛋白的表达。哇巴因注射数周后，INL外边界的BrdU阳性细胞表达Prox1和钙结合蛋白D-28k，这两种蛋白是HC的特异性标志物。综上所述，这些结果表明哺乳动物的视网膜能够在体内再生新型中间神经元（HC），这增进了我们对哺乳动物视网膜损伤后再生的理解。
