Wayne State University School of Medicine, Department of Ophthalmology, Visual and Anatomical Sciences, Detroit, MI, USA.
Wayne State University School of Medicine, Department of Ophthalmology, Visual and Anatomical Sciences, Detroit, MI, USA; Wayne State University School of Medicine, Center for Molecular Medicine and Genetics, Detroit, MI, USA.
Exp Eye Res. 2021 Aug;209:108630. doi: 10.1016/j.exer.2021.108630. Epub 2021 May 21.
Zebrafish (Danio rerio) have become a highly-utilized model system in the field of regenerative biology because of their endogenous ability to regenerate many tissues and organs, including the retina. The vast majority of previous research on retinal regeneration in adult zebrafish utilizes acute methodologies for retinal damage. Acute retinal cell death triggers a reactive gliosis response of Müller glia (MG), the resident macroglia of the retina. In addition, each activated MG undergoes asymmetric cell division to produce a neuronal progenitor, which continues to divide and ultimately gives rise to new retinal neurons. Studies using these approaches have uncovered many crucial mechanisms by which MG respond to acute damage. However, they may not adequately mimic the chronic neuronal degeneration observed in many human retinal degenerative diseases. The current study aimed to develop a new long-term, chronic photoreceptor damage and degeneration model in adult zebrafish. Comparing the subsequent cellular responses to that of the commonly-used acute high-intensity model, we found that low, continuous light exposure damaged the outer segments of both rod and cone photoreceptors, but did not result in significant apoptotic cell death, MG gliosis, or MG cell-cycle re-entry. Instead, chronic light nearly completely truncated photoreceptor outer segments and resulted in a recruitment of microglia to the area. Together, these studies present a chronic photoreceptor model that can be performed in a relatively short time frame (21 days), that may lend insight into the cellular events underlying non-regenerative photoreceptor degeneration observed in other model systems.
斑马鱼（Danio rerio）由于其内在的再生许多组织和器官的能力，包括视网膜，已成为再生生物学领域中高度利用的模型系统。以前大多数关于成年斑马鱼视网膜再生的研究都利用急性视网膜损伤方法。急性视网膜细胞死亡会引发 Müller 胶质细胞（MG）的反应性神经胶质增生反应，MG 是视网膜的固有大胶质细胞。此外，每个活化的 MG 都会进行不对称细胞分裂，产生一个神经元祖细胞，该祖细胞继续分裂，最终产生新的视网膜神经元。使用这些方法的研究揭示了 MG 对急性损伤的许多关键反应机制。然而，它们可能无法充分模拟许多人类视网膜退行性疾病中观察到的慢性神经元变性。本研究旨在开发一种新的成年斑马鱼长期慢性光感受器损伤和变性模型。将随后的细胞反应与常用的急性高强度模型进行比较，我们发现，低强度、连续光照会损伤杆状和锥状光感受器的外节，但不会导致明显的细胞凋亡、MG 神经胶质增生或 MG 细胞周期重新进入。相反，慢性光照几乎完全截断了光感受器的外节，并导致小胶质细胞招募到该区域。总之，这些研究提出了一种慢性光感受器模型，该模型可以在相对较短的时间内完成（21 天），可能有助于深入了解在其他模型系统中观察到的非再生性光感受器变性的细胞事件。
