Antibodies Against Lysophosphatidic Acid Protect Against Blast-Induced Ocular Injuries.
Antibodies Against Lysophosphatidic Acid Protect Against Blast-Induced Ocular Injuries.
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DOI：
10.3389/fneur.2020.611816
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发表时间：
2020
影响因子：
3.4
通讯作者：
Long JB
中科院分区：
文献类型：
--
作者：
Arun P;Rossetti F;DeMar JC;Wang Y;Batuure AB;Wilder DM;Gist ID;Morris AJ;Sabbadini RA;Long JB
暴露于爆炸超压波是参与最近的战斗行动的退伍军人眼部损伤和由此产生的视觉功能障碍的主要原因。迄今为止，尚未开发出有效的治疗策略来治疗爆炸引起的眼功能障碍。溶血磷脂酸（LPA）是由活化的血小板、星形胶质细胞、脉络丛细胞和小胶质细胞产生的生物活性磷脂，并且据报道在刺激炎症过程中起主要作用。据报道，在患有创伤性脑损伤（TBI）的患者中以及在小鼠的受控皮质撞击（CCI）TBI模型中，脑脊液中的LPA水平急剧增加。在本研究中，我们评估了单克隆LPA抗体（25 mg/kg）的单次静脉给药的效力，在1小时后爆炸保护对视网膜损伤和相关的眼部功能障碍。我们的研究结果表明，一个单一的19 psi爆炸暴露显着增加了血浆中的几种LPA在1和4小时后爆炸的水平。抗LPA抗体处理显著降低了神经胶质细胞活化，并在冲击波暴露后第8天保留了视网膜中的神经元细胞形态。视动力学测量表明，抗LPA抗体治疗显着改善视力在两个眼睛在第2和第6天后爆炸曝光。抗LPA抗体处理在爆炸暴露后第7天显著增加双眼中的视杆光感受器和双极神经元细胞信号传导。这些结果表明，冲击波暴露触发释放的LPA，这起着促进冲击波诱导的眼损伤的主要作用，和一个单一的早期管理的抗LPA抗体提供了显着的保护。
Exposure to blast overpressure waves is implicated as the major cause of ocular injuries and resultant visual dysfunction in veterans involved in recent combat operations. No effective therapeutic strategies have been developed so far for blast-induced ocular dysfunction. Lysophosphatidic acid (LPA) is a bioactive phospholipid generated by activated platelets, astrocytes, choroidal plexus cells, and microglia and is reported to play major roles in stimulating inflammatory processes. The levels of LPA in the cerebrospinal fluid have been reported to increase acutely in patients with traumatic brain injury (TBI) as well as in a controlled cortical impact (CCI) TBI model in mice. In the present study, we have evaluated the efficacy of a single intravenous administration of a monoclonal LPA antibody (25 mg/kg) given at 1 h post-blast for protection against injuries to the retina and associated ocular dysfunctions. Our results show that a single 19 psi blast exposure significantly increased the levels of several species of LPA in blood plasma at 1 and 4 h post-blast. The anti-LPA antibody treatment significantly decreased glial cell activation and preserved neuronal cell morphology in the retina on day 8 after blast exposure. Optokinetic measurements indicated that anti-LPA antibody treatment significantly improved visual acuity in both eyes on days 2 and 6 post-blast exposure. Anti-LPA antibody treatment significantly increased rod photoreceptor and bipolar neuronal cell signaling in both eyes on day 7 post-blast exposure. These results suggest that blast exposure triggers release of LPAs, which play a major role promoting blast-induced ocular injuries, and that a single early administration of anti-LPA antibodies provides significant protection.
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影响因子：
2.9
作者：
Fincher J;Whiteneck C;Birgbauer E
通讯作者：
Birgbauer E
影响因子：
3.4
作者：
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通讯作者：
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6.2
作者：
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通讯作者：
Chun, Jerold
影响因子：
3.8
作者：
Jiang, Youde;Pagadala, Jayaprakash;Steinle, Jena J.
通讯作者：
Steinle, Jena J.