Ranski Alexandra H, Kramer Ashley C, Morgan Gregory W, Perez Jennifer L, Thummel Ryan
Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USA.
PeerJ. 2018 Sep 20;6:e5646. doi: 10.7717/peerj.5646. eCollection 2018.
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 and 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.
斑马鱼视网膜中的穆勒胶质细胞通过重新进入细胞周期对视网膜损伤作出反应，这会产生大量视网膜祖细胞，最终替代丢失的神经元。在本研究中，我们比较了接受一轮光毒性处理的成年斑马鱼与接受连续六轮光毒性处理的成年斑马鱼的再生结果。我们观察到，在接受多轮光毒性光照的斑马鱼中，穆勒胶质细胞继续重新进入细胞周期以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，在光损伤36小时时，接受多轮损伤的视网膜比接受第一轮光损伤的视网膜表现出更大程度的光感受器损失。此外，我们发现，在接受多轮光处理的视网膜中，穆勒胶质细胞的急性胶质细胞反应似乎有所增加。这表现为细胞肥大、GFAP细胞定位的变化以及[具体物质]和[具体物质]表达的短暂增加。最后，在第六轮光毒性损伤后，我们观察到在内网状层和外视网膜中，错误定位的HuC/D阳性无长突细胞和神经节细胞显著增加，并且再生的蓝色视锥光感受器数量减少。这些数据补充了最近的研究发现，即成年斑马鱼的视网膜再生与穆勒胶质细胞反应性同时发生，并可能导致异常神经元的产生。这些数据也是首次证明，穆勒胶质细胞似乎会响应多轮光毒性损伤而改变其表型，在保持显著的光感受器长期再生能力的同时，急性胶质细胞增生增加。
