Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy.

IF 4.3 3区 医学 Q2 CHEMISTRY, MEDICINAL
Pharmaceuticals Pub Date : 2025-06-19 DOI:10.3390/ph18060920
Nicolás S Ciranna, Ronan Nakamura, Rafael Peláez, Álvaro Pérez-Sala, Patricia Sarrión, Juan C Fernández, Alejandra Paganelli, Agustín P Aranalde, Ulises P Ruiz, Juan J López-Costa, César F Loidl, Alfredo Martínez, Manuel Rey-Funes
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引用次数: 0

Abstract

Background: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal model of TON. Methods: The left eyes of Wistar rats were subjected to intraorbital nerve crush (IONC) while the right ones were sham operated. The group of rats treated with MB (n = 16) received five intraperitoneal injections with 2.0 mg/kg MB in the 24 h following IONC while the control group (n = 16) received just vehicle (PBS) as a control. Twenty-one days after surgery, scotopic full field (scERG), scotopic oscillatory potentials (OP), photopic full field (phERG) and pattern (PERG) electroretinography were performed for retinal function assessment. Furthermore, the number of cell nuclei in the ganglion cell layer (GCL) was recorded in post mortem histological sections. Results: IONC induced very significant reductions in electrophysiological parameters including scotopic a- and b-wave, OPs, photopic b-wave, PhNR amplitude and N2 amplitude. In addition, it also generated a significant prolongation of the N2 implicit time, indicating a profound impact on retinal function. This was further corroborated by a very significant reduction in the number of neuronal nuclei in the GCL, suggesting an intense loss and functional impairment of retinal ganglion cells. MB treatment was able to prevent, partially or completely, all those parameters, indicating the efficiency of such approach. Conclusions: Since MB is already approved for clinical use and presents a high safety profile, it could be repurposed as a neuroprotective drug for ophthalmological applications once proper phase 2 clinical trials are accomplished.

亚甲基蓝对创伤性视神经病变大鼠模型的神经保护作用。
背景:外伤性视神经病变(TON)是世界范围内视力丧失的主要原因,治疗选择有限。在这里,我们研究了亚甲基蓝(MB),一种自由基清除剂,是否能够在TON动物模型中预防神经病变的形态学和电生理特征。方法:采用Wistar大鼠左眼行眶内神经压迫术,右眼行假手术。MB组(n = 16)在IONC后24 h内5次腹腔注射2.0 mg/kg MB,对照组(n = 16)只注射培养液(PBS)作为对照。术后21 d行暗位全视野(scERG)、暗位振荡电位(OP)、光位全视野(phERG)和模式(PERG)视网膜电图评估视网膜功能。死后病理切片记录神经节细胞层(GCL)细胞核数量。结果:离子诱导的电生理参数包括暗a波和b波、OPs、光b波、PhNR振幅和N2振幅均显著降低。此外,它还使N2隐隐时间明显延长,表明对视网膜功能有深远的影响。GCL中神经元核数量的显著减少进一步证实了这一点,表明视网膜神经节细胞的严重损失和功能损伤。MB治疗能够部分或完全预防所有这些参数,表明这种方法的有效性。结论:由于MB已经被批准临床使用,并且具有很高的安全性,一旦完成适当的2期临床试验,它可以被重新用作眼科应用的神经保护药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmaceuticals
Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍: Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.
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