光生物调节作为内耳潜在再生信号：将线粒体氧化还原信号与细胞命运调控相联系

文献信息

中文摘要

光生物调节（PBM）是一种非热治疗方式，利用低强度红光或近红外光调节生物活动。内耳实验研究报告了听觉神经元保存、前庭损伤减轻、移植干细胞存活改善以及耳器官样体分化改变。这些观察提示，PBM除提供细胞保护外，还可能影响分化相关的细胞状态。经典机制模型提出，光子与线粒体发色团（尤其是细胞色素c氧化酶）相互作用，导致呼吸、ATP、活性氧（ROS）、一氧化氮、钙及下游信号改变；然而，尚未确立普遍的主要光受体。在一项2020年小鼠胚胎干细胞来源耳器官样体研究中，PBM与更多器官样体样结构、毛细胞相关标志物增加、ROS升高及Hes5表达降低相关。RNA测序比较将五个胚状体合并为每个条件一个样本，限制了生物学重复和统计推断。因此，Hes5结果应视为探索性，并不能证明直接抑制Notch。其他再生组织的研究显示，PBM可激活ROS依赖的PI3K/AKT/GSK3β/β-catenin信号，这提供了机制先例而非内耳的证据。因此，本综述提出一个可检验的工作模型：在耳分化过程中，PBM可能将线粒体和氧化还原反应与Wnt/β-catenin及Notch/HES5通路联系起来，同时强调成熟毛细胞再生、新SGN生成和听力恢复尚未确立。

英文摘要

Photobiomodulation (PBM) is a non-thermal therapeutic modality in which low-intensity red or near-infrared light is used to modulate biological activity. Experimental inner-ear studies report preservation of auditory neurons, attenuation of vestibular injury, improved survival of transplanted stem cells, and changes in otic organoid differentiation. These observations raise the possibility that PBM may influence differentiation-associated cellular states in addition to providing cytoprotection. The classical mechanistic model proposes that photons interact with mitochondrial chromophores, particularly cytochrome c oxidase, leading to changes in respiration, ATP, reactive oxygen species (ROS), nitric oxide, calcium, and downstream signaling; however, a universal primary photoreceptor has not been established. In a 2020 mouse embryonic-stem-cell-derived otic-organoid study, PBM was associated with more organoid-like structures, increased hair-cell-associated markers, increased ROS, and lower Hes5 expression. The RNA-sequencing comparison pooled five embryoid bodies into one sample per condition, limiting biological replication and statistical inference. Accordingly, the Hes5 result should be regarded as exploratory and does not demonstrate direct Notch inhibition. Studies in other regenerative tissues show that PBM can engage ROS-dependent PI3K/AKT/GSK3β/β-catenin signaling, providing a mechanistic precedent rather than proof for the inner ear. This review therefore presents a testable working model in which PBM may connect mitochondrial and redox responses to Wnt/β-catenin and Notch/HES5 pathways during otic differentiation, while emphasizing that mature hair-cell regeneration, new SGN generation, and hearing restoration have not yet been established.