Department of Anatomy and Neurobiology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Department of Ophthalmology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Sci Rep. 2024 Jan 2;14(1):61. doi: 10.1038/s41598-023-50485-7.
Animal models for retinal degeneration are essential for elucidating its pathogenesis and developing new therapeutic strategies in humans. N-methyl-N-nitrosourea (MNU) has been extensively used to construct a photoreceptor-specific degeneration model, which has served to unveil the molecular process of photoreceptor degeneration as well as the mechanisms regulating the protective responses of remaining cells. Methyl methanesulphonate (MMS), also known to cause photoreceptor degeneration, is considered a good alternative to MNU due to its higher usability; however, detailed pathophysiological processes after MMS treatment remain uncharacterized. Here, we analyzed the time course of photoreceptor degeneration, Müller glial proliferation, and expression of secretory factors after MNU and MMS treatments in rats. While the timing of rod degeneration was similar between the treatments, we unexpectedly found that cones survived slightly longer after MMS treatment. Müller glia reentered the cell cycle at a similar timing after the two treatments; however, the G1/S transition occurred earlier after MMS treatment. Moreover, growth factors such as FGF2 and LIF were more highly upregulated in the MMS model. These data suggest that comparative analyses of the two injury models may be beneficial for understanding the complex regulatory mechanisms underlying the proliferative response of Müller glia.
用于视网膜退行性变的动物模型对于阐明其发病机制和在人类中开发新的治疗策略至关重要。N-甲基-N-亚硝脲（MNU）已被广泛用于构建光感受器特异性退行性变模型，该模型揭示了光感受器退行性变的分子过程以及调节剩余细胞保护反应的机制。甲磺酸甲酯（MMS）也被认为是 MNU 的良好替代品，因为它的可用性更高，可导致光感受器退行性变，但 MMS 治疗后的详细病理生理过程仍未得到阐明。在这里，我们分析了 MNU 和 MMS 处理后大鼠光感受器退行性变、Müller 胶质细胞增殖和分泌因子表达的时间过程。虽然两种处理方式的 rod 退行性变时间相似，但我们出人意料地发现 MMS 处理后 cones 存活时间略长。两种处理后 Müller 胶质细胞在相似的时间重新进入细胞周期；然而，MMS 处理后 G1/S 过渡更早发生。此外，FGF2 和 LIF 等生长因子在 MMS 模型中被高度上调。这些数据表明，对两种损伤模型的比较分析可能有助于理解 Müller 胶质细胞增殖反应背后的复杂调节机制。
