Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma.
Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma.
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DOI：
10.1038/s41598-021-96107-y
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发表时间：
2021-08-19
影响因子：
4.6
通讯作者：
Ahmed Z
中科院分区：
文献类型：
--
作者：
Thomas CN;Bernardo-Colón A;Courtie E;Essex G;Rex TS;Blanch RJ;Ahmed Z
低超压冲击波暴露可导致眼部反复性空气冲击伤，且常反复发生，且连续性较强。我们已经证明，半胱天冬酶-2导致视网膜神经节细胞（RGC）的钝性眼外伤后死亡。在此，我们研究了在空气冲击波诱导的间接创伤性视神经病变（b-ITON）小鼠模型中caspase-2是否也介导RGC凋亡。将C57 BL/6小鼠暴露于重复的超压空气冲击（3 × 2 × 15 psi），并在第一次2 × 15 psi后5小时（“冲击后”）或第一次冲击暴露前48小时（“冲击前”）玻璃体内注射针对胱天蛋白酶-2（siCASP 2）或针对对照增强型绿色荧光蛋白（siEGFP）的siRNA，每7天重复一次。RGC计数不受b-ITON或玻璃体内注射的影响，尽管退化的ON轴突增加，即使在siCASP 2“后胚”注射组中也是如此。在b-ITON和玻璃体内siCASP 2“胚前”注射后，退化的ON轴突保持在假手术水平，但与siEGFP处理的眼睛相比，siCASP 2中的退化轴突较少。“胚后”玻璃体内注射引起更大的玻璃体炎症，由siCASP 2增强，而在“胚前”注射的眼睛中较少，这被siCASP 2消除。我们得出结论，眼外伤后玻璃体内注射时机诱导可变的视网膜和ON病理学，破坏了我们的候选神经保护疗法siCASP 2。
Ocular repeated air blast injuries occur from low overpressure blast wave exposure, which are often repeated and in quick succession. We have shown that caspase-2 caused the death of retinal ganglion cells (RGC) after blunt ocular trauma. Here, we investigated if caspase-2 also mediates RGC apoptosis in a mouse model of air blast induced indirect traumatic optic neuropathy (b-ITON). C57BL/6 mice were exposed to repeated blasts of overpressure air (3 × 2 × 15 psi) and intravitreal injections of siRNA against caspase-2 (siCASP2) or against a control enhanced green fluorescent protein (siEGFP) at either 5 h after the first 2 × 15 psi (“post-blast”) or 48 h before the first blast exposure (“pre-blast”) and repeated every 7 days. RGC counts were unaffected by the b-ITON or intravitreal injections, despite increased degenerating ON axons, even in siCASP2 “post-blast” injection groups. Degenerating ON axons remained at sham levels after b-ITON and intravitreal siCASP2 “pre-blast” injections, but with less degenerating axons in siCASP2 compared to siEGFP-treated eyes. Intravitreal injections “post-blast” caused greater vitreous inflammation, potentiated by siCASP2, with less in “pre-blast” injected eyes, which was abrogated by siCASP2. We conclude that intravitreal injection timing after ocular trauma induced variable retinal and ON pathology, undermining our candidate neuroprotective therapy, siCASP2.
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