Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Curr Eye Res. 2021 Apr;46(4):558-567. doi: 10.1080/02713683.2020.1808999. Epub 2020 Sep 4.
Lithium is an old drug to control bipolar disorder. Moreover, it presents neuroprotective effects and supports neuronal plasticity. The aim of this study was to evaluate neuroprotective effect of intravitreal lithium after optic nerve injury.
Three dosages of lithium chloride, including 2 pmol, 200 pmol, and 2 nmol, were injected intravitreally after rat optic nerve injury. Proteins expression were assessed by western blot. Nitric oxide (NO) metabolites were measured by Griess test. Visual evoked potential (VEP) and optical coherence tomography (OCT) measurement were performed after trauma induction, in addition to H & E and TUJ1 staining of ganglion cells.
Western blot depicted lithium can significantly increase antiapoptotic Bcl-2 protein level and reduce -ERK, Toll-like receptor 4 (TLR4) and proapoptotic proteins such as Bax level in retinal tissue and Griess test reflected that NO metabolites level decreased in lithium treated eyes ( < .05). While, OCT showed no significant changes ( = .36 and = .43 comparing treated group with trauma) in retinal ganglion cell layer thickness after lithium injection, VEP P2 wave amplitude increased significantly ( < .01) in lithium-treated eyes and its latency reduced ( < .05 for N1 wave and < .01 for P2 wave). Tuj1 antibody-labeled retinal ganglion cells analyzing showed that the number of retinal ganglion cells were significantly higher in lithium treated eyes compared to untreated eyes with optic nerve injury.
It seems intravitreally lithium has optic nerve neuroprotective effects by various mechanisms like overexpression of antiapoptotic proteins, suppressing proinflammatory molecules and proapoptotic factors, and decreasing nitric oxide.
锂是一种控制双相情感障碍的老药。此外，它具有神经保护作用并支持神经元可塑性。本研究旨在评估玻璃体内锂对视神经损伤后的神经保护作用。
在大鼠视神经损伤后，玻璃体内注射三种剂量的氯化锂，包括 2 pmol、200 pmol 和 2 nmol。通过 Western blot 评估蛋白质表达。通过格里斯试验测量一氧化氮（NO）代谢物。在创伤诱导后进行视觉诱发电位（VEP）和光相干断层扫描（OCT）测量，以及神经节细胞的 H&E 和 TUJ1 染色。
Western blot 表明，锂可显著增加视网膜组织中抗凋亡 Bcl-2 蛋白水平，并降低 -ERK、Toll 样受体 4（TLR4）和促凋亡蛋白如 Bax 水平（ < 0.05）。而 Griess 试验反映锂处理眼的 NO 代谢物水平降低（ < 0.05）。然而，玻璃体内注射锂后 OCT 显示视网膜神经节细胞层厚度无明显变化（与创伤组相比， = 0.36 和 = 0.43），VEP P2 波振幅显著增加（ < 0.01），潜伏期缩短（N1 波 < 0.05，P2 波 < 0.01）。Tuj1 抗体标记的视网膜神经节细胞分析表明，与未治疗的视神经损伤眼相比，锂处理眼的视网膜神经节细胞数量明显更高。
玻璃体内注射锂似乎通过多种机制具有视神经神经保护作用，如抗凋亡蛋白的过表达、抑制促炎分子和促凋亡因子以及降低一氧化氮。
