Primary blast injury (caused by the initial rapid increase in pressure following an explosive blast) to the retina and optic nerve (ON) causes progressive visual loss and neurodegeneration. Military personnel are exposed to multiple low-overpressure blast waves, which may be in quick succession, such as during breacher training or in combat. We investigated the necroptotic cell death pathway in the retina in a mouse repeated primary ocular blast injury (rPBI) model using immunohistochemistry. We further evaluated whether intravitreal injections of a potent necroptosis inhibitor, Necrostatin-1s (Nec-1s), protects the retina and ON axons by retinal ganglion cells (RGC) counts, ON axonal counting and optical coherence tomography (OCT) analysis of vitreous haze. Receptor interacting protein kinase (RIPK) 3, increased in the inner plexiform layer 2 days post injury (dpi) and persisted until 14 dpi, whilst RIPK1 protein expression did not change after injury. The number of degenerating ON axons was increased at 28 dpi but there was no evidence of a reduction in the number of intact ON axons or RNA-binding protein with multiple splicing (RBPMS)⁺ RGC in the retina by 28 dpi in animals not receiving any intravitreal injections. But, when intravitreal injections (vehicle or Nec-1s) were given there was a significant reduction in RBPMS⁺ RGC numbers, suggesting that rPBI with intraocular injections is damaging to RGC. There were fewer RGC lost after Nec-1s than vehicle injection, but there was no effect of Nec-1s or vehicle treatment on the number of degenerating axons. OCT analysis demonstrated no effect of rPBI on vitreous haze, but intravitreal injection combined with rPBI increased vitreous haze (P = 0.004). Whilst necroptosis may be an active cell death signalling pathway after rPBI, its inhibition did not prevent cell death, and intravitreal injections in combination with rPBI increased vitreous inflammation and reduced RBPMS⁺ RGC numbers, implying intravitreal injection is not an ideal method for drug delivery after rPBI.

视网膜和视神经 (ON) 的原发性爆炸损伤（由爆炸性爆炸后最初的压力迅速增加引起）会导致进行性视力丧失和神经变性。军事人员会暴露在多个低超压冲击波中，这些冲击波可能会快速连续发生，例如在破坏者训练或战斗中。我们使用免疫组织化学研究了小鼠重复原发性眼部爆炸损伤 (rPBI) 模型中视网膜中的坏死性细胞死亡途径。我们进一步评估了玻璃体内注射有效的坏死性凋亡抑制剂 Necrostatin-1s (Nec-1s) 是否通过视网膜神经节细胞 (RGC) 计数、ON 轴突计数和玻璃体混浊的光学相干断层扫描 (OCT) 分析保护视网膜和 ON 轴突. 受体相互作用蛋白激酶（RIPK）3，损伤后 2 天 (dpi) 在内丛状层中增加并持续到 14 dpi，而 RIPK1 蛋白表达在损伤后没有变化。退化 ON 轴突的数量在 28 dpi 时增加，但没有证据表明完整 ON 轴突或具有多重剪接 (RBPMS) 的 RNA 结合蛋白的数量减少⁺ 28 dpi 在未接受任何玻璃体内注射的动物中视网膜中的 RGC。但是，当给予玻璃体内注射（车辆或 Nec-1s）时，RBPMS ⁺ RGC 数量显着减少，表明眼内注射的 rPBI 对 RGC 有害。Nec-1s 后的 RGC 丢失比注射媒介物少，但 Nec-1s 或媒介物治疗对退化轴突的数量没有影响。OCT 分析表明 rPBI 对玻璃体混浊没有影响，但玻璃体内注射结合 rPBI 增加了玻璃体混浊（P = 0.004）。虽然坏死性凋亡可能是 rPBI 后一个活跃的细胞死亡信号通路，但它的抑制并不能阻止细胞死亡，玻璃体内注射与 rPBI 联合增加了玻璃体炎症并降低了 RBPMS⁺ RGC 数字，这意味着玻璃体内注射不是 rPBI 后给药的理想方法。