Pressure waves from explosions or other traumatic events can damage the neurons of the eye and visual centers of the brain, leading to functional loss of vision. There are currently few treatments for such injuries that can be deployed rapidly to mitigate damage. Brain-derived neurotrophic factor (BDNF) and activation of its receptor tropomycin-related kinase B (TrkB) have neuroprotective effects in a number of degeneration models. Small molecule activators of TrkB, such as N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC), cross the blood–brain and blood-retina barriers after systemic administration. We characterize the effects of blast-induced ocular trauma on retinal and visual function. We show that systemic administration of HIOC, a potent small molecule activator of the BDNF/TrkB receptor, preserves visual function in mice exposed to ocular blast injury. The HIOC treatment for one week preserves visual function for at least four months. The HIOC treatment effectively protected vision when the initial dose was administered up to 3 h after blast, but not if the initial treatment was delayed for 24 h. We provide evidence that the therapeutic effect of HIOC is mediated by activation of BDNF/TrkB receptors. The results indicate that HIOC may be useful for managing ocular blast injury and other forms of traumatic optic neuropathy.

中文翻译：

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用于治疗眼部爆炸引起的视力丧失的原霉素相关激酶 B 受体激活剂


爆炸或其他创伤事件产生的压力波会损害眼睛的神经元和大脑的视觉中心，导致功能性视力丧失。目前，针对此类损伤的治疗方法很少，可以快速部署以减轻损害。脑源性神经营养因子 (BDNF) 及其受体原霉素相关激酶 B (TrkB) 的激活在许多退化模型中具有神经保护作用。 TrkB 的小分子激活剂，例如 N-[2-(5-羟基-1H-吲哚-3-基)乙基]-2-氧代哌啶-3-甲酰胺 (HIOC)，可以穿过血脑和血视网膜屏障全身给药后。我们描述了爆炸引起的眼外伤对视网膜和视觉功能的影响。我们发现，全身给予 HIOC（一种 BDNF/TrkB 受体的有效小分子激活剂）可以保护遭受眼爆炸损伤的小鼠的视觉功能。 HIOC 治疗一周可将视觉功能保留至少四个月。当初始剂量在爆炸后 3 小时内施用时，HIOC 治疗可有效保护视力，但如果初始治疗延迟 24 小时则无效。我们提供的证据表明 HIOC 的治疗效果是通过 BDNF/TrkB 受体的激活介导的。结果表明，HIOC 可能有助于治疗眼冲击损伤和其他形式的外伤性视神经病变。