Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion.
Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion.
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作者：
Ranski AH;Kramer AC;Morgan GW;Perez JL;Thummel R
斑马鱼视网膜中的穆勒胶质细胞通过重新进入细胞周期来应对视网膜损伤，从而产生大量的视网膜前体细胞，最终取代丢失的神经元。在这项研究中，我们比较了成年斑马鱼暴露于一轮光毒治疗与成年斑马鱼暴露于连续六轮光毒治疗的再生结果。我们观察到，在暴露于多轮光毒光下的斑马鱼中，Müler胶质细胞继续重新进入细胞周期，产生视网膜祖细胞簇。然而，也注意到了一些异常情况。首先，我们发现，暴露在多轮损伤中的视网膜在36小时的光损伤中表现出比暴露在第一轮光损伤中的视网膜更大的光感受器损失。此外，我们发现，在暴露于多轮光治疗的视网膜中，米勒胶质细胞似乎有急性胶质细胞反应的增加。这表现为细胞肥大，GFAP细胞定位的改变，以及STAT3和GFAP表达的一过性增加。最后，在第六轮光毒性损伤后，我们观察到错误定位的Huc/D阳性的无长突细胞和神经节细胞在内丛状层和外视网膜显著增加，再生的蓝色视锥感光细胞数量减少。这些数据补充了最近的发现，即成年斑马鱼的视网膜再生伴随着Müler胶质细胞的反应，并可能导致异常神经元的产生。这些数据也首次证明，Müler胶质细胞似乎改变了它们的表型，以响应多轮光毒损伤，表现出急性胶质细胞增多，同时保持了显著的光感受器长期再生能力。
Müller glia in the zebrafish retina respond to retinal damage by re-entering the cell cycle, which generates large numbers of retinal progenitors that ultimately replace the lost neurons. In this study we compared the regenerative outcomes of adult zebrafish exposed to one round of phototoxic treatment with adult zebrafish exposed to six consecutive rounds of phototoxic treatment. We observed that Müller glia continued to re-enter the cell cycle to produce clusters of retinal progenitors in zebrafish exposed to multiple rounds of phototoxic light. Some abnormalities were noted, however. First, we found that retinas exposed to multiple rounds of damage exhibited a greater loss of photoreceptors at 36 hours of light damage than retinas that were exposed to their first round of light damage. In addition, we found that Müller glia appeared to have an increase in the acute gliotic response in retinas exposed to multiple rounds of light treatment. This was evidenced by cellular hypertrophy, changes in GFAP cellular localization, and transient increases in stat3 and gfap expression. Finally, following the sixth round of phototoxic lesion, we observed a significant increase in mis-localized HuC/D-positive amacrine and ganglion cells in the inner plexiform layer and outer retina, and a decreased number of regenerated blue cone photoreceptors. These data add to recent findings that retinal regeneration in adult zebrafish occurs concomitant with Müller glia reactivity and can result in the generation of aberrant neurons. These data are also the first to demonstrate that Müller glia appear to modify their phenotype in response to multiple rounds of phototoxic lesion, exhibiting an increase in acute gliosis while maintaining a remarkable capacity for long-term regeneration of photoreceptors.
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斑马鱼müller神经胶质衍生的祖细胞是多能，表现出增殖偏见和再生过多的神经元。
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