Assessment of necroptosis in the retina in a repeated primary ocular blast injury mouse model.
Assessment of necroptosis in the retina in a repeated primary ocular blast injury mouse model.
复制标题
反复原发性眼细胞损伤小鼠模型视网膜坏死性上睑下垂的评估。
DOI：
10.1016/j.exer.2020.108102
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发表时间：
2020-08
影响因子：
3.4
通讯作者：
Blanch RJ
中科院分区：
文献类型：
--
作者：
Thomas CN;Courtie E;Bernardo-Colón A;Essex G;Rex TS;Ahmed Z;Blanch RJ
对视网膜和视神经（ON）的原发性冲击伤（由爆炸性爆炸后压力的初始快速增加引起）导致进行性视力丧失和神经变性。军事人员暴露于多个低超压冲击波，这些冲击波可能是快速连续的，例如在破坏者训练或战斗期间。我们采用免疫组织化学方法研究了小鼠反复原发性眼冲击伤（rPBI）模型中视网膜坏死性细胞死亡途径。我们进一步评估了玻璃体内注射一种有效的坏死性凋亡抑制剂Necrostatin-1 s（Nec-1 s）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）分析来保护视网膜和ON轴突。受体相互作用蛋白激酶（RIPK）3在损伤后2天（dpi）在内网状层中增加并持续至14 dpi，而RIPK 1蛋白表达在损伤后没有改变。退化的ON轴突的数量在28 dpi时增加，但在未接受任何玻璃体内注射的动物中，到28 dpi时，没有证据表明视网膜中完整的ON轴突或具有多重剪接的RNA结合蛋白（RBPMS）+ RGC的数量减少。但是，当给予玻璃体内注射（溶剂或Nec-1）时，RBPMS+ RGC数量显着减少，这表明眼内注射的rPBI对RGC有损害。Nec-1 s注射后RGC的丢失比溶媒注射后少，但Nec-1 s或溶媒治疗对变性轴突的数量没有影响。OCT分析显示rPBI对玻璃体混浊无影响，但玻璃体内注射联合rPBI增加玻璃体混浊（P = 0.004）。虽然坏死性凋亡可能是rPBI后的活性细胞死亡信号传导途径，但其抑制并不能阻止细胞死亡，并且玻璃体内注射与rPBI组合增加了玻璃体炎症并减少了RBPMS+ RGC数量，这意味着玻璃体内注射不是rPBI后药物递送的理想方法。
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.
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影响因子：
3.4
作者：
Kokona, Despina;Haner, Nathanael U.;Zinkernagel, Martin S.
通讯作者：
Zinkernagel, Martin S.
影响因子：
9
作者：
Cougnoux A;Cluzeau C;Mitra S;Li R;Williams I;Burkert K;Xu X;Wassif CA;Zheng W;Porter FD
通讯作者：
Porter FD
影响因子：
3.4
作者：
Mead, Ben;Tomarev, Stanislav
通讯作者：
Tomarev, Stanislav
影响因子：
3.7
作者：
Mead B;Thompson A;Scheven BA;Logan A;Berry M;Leadbeater W
通讯作者：
Leadbeater W
影响因子：
4.4
作者：
Bricker-Anthony, Courtney;Hines-Beard, Jessica;Rex, Tonia S.
通讯作者：
Rex, Tonia S.