Ryan Annie K, Asemota Brooke I, Heisler-Taylor Tyler, Mello Claire, Rodriguez Luis, Sponsel William E, Racine Julie, Rex Tonia S, Glickman Randolph D, Reilly Matthew A
Department of Biomedical Engineering, The Ohio State University, Columbus, OH, United States of America.
Division of Neurology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States of America.
PLoS One. 2025 Jan 16;20(1):e0312220. doi: 10.1371/journal.pone.0312220. eCollection 2025.
Traumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone. This is due in part to the lack of translational animal models suitable for understanding mechanisms and evaluating candidate treatments. In this study, we developed a rat model of TON in which the eye is rapidly rotated, inflicting mechanical stress on the optic nerve and leading to significant visual deficits. These functional deficits were thoroughly characterized up to one week after injury using electrophysiology and immunohistochemistry. The photopic negative response (PhNR) of the light adapted full field electroretinogram (LA ffERG) was significantly altered following injury. This correlated with increased biomarkers of retinal stress, axon disruption, and cell death. Together, this evidence suggests the utility of our model for mimicking clinically relevant TON and that the PhNR may be an early diagnostic for TON. Future studies will utilize this animal model for evaluation of candidate treatments.
创伤性视神经病变（TON）是头部受伤后不可逆失明的常见原因。TON的特征是视神经轴突损伤，随后在损伤后的数天和数周内视网膜神经节细胞死亡。目前，尚未发现任何治疗或手术方法能比单纯观察带来更多益处。部分原因是缺乏适用于理解机制和评估候选治疗方法的转化动物模型。在本研究中，我们开发了一种TON大鼠模型，通过快速旋转眼睛对视神经施加机械应力，导致明显的视觉缺陷。使用电生理学和免疫组织化学方法对损伤后长达一周的这些功能缺陷进行了全面表征。损伤后，光适应全视野视网膜电图（LA ffERG）的明视负反应（PhNR）发生了显著改变。这与视网膜应激、轴突破坏和细胞死亡的生物标志物增加相关。总之，这些证据表明我们的模型可用于模拟临床相关的TON，并且PhNR可能是TON的早期诊断指标。未来的研究将利用这种动物模型评估候选治疗方法。
