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在高血压性青光眼小鼠模型中,烟酸与胞磷胆碱联合给药后视网膜生理功能得以恢复。

Restored retinal physiology after administration of niacin with citicoline in a mouse model of hypertensive glaucoma.

作者信息

Melecchi Alberto, Amato Rosario, Dal Monte Massimo, Rusciano Dario, Bagnoli Paola, Cammalleri Maurizio

机构信息

Department of Biology, University of Pisa, Pisa, Italy.

Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.

出版信息

Front Med (Lausanne). 2023 Sep 5;10:1230941. doi: 10.3389/fmed.2023.1230941. eCollection 2023.

Abstract

INTRODUCTION

Much interest has been addressed to antioxidant dietary supplements that are known to lower the risk of developing glaucoma or delay its progression. Among them, niacin and citicoline protect retinal ganglion cells (RGCs) from degeneration by targeting mitochondria, though at different levels. A well-established mouse model of RGC degeneration induced by experimental intraocular pressure (IOP) elevation was used to investigate whether a novel combination of niacin/citicoline has better efficacy over each single component in preserving RGC health in response to IOP increase.

METHODS

Ocular hypertension was induced by an intracameral injection of methylcellulose that clogs the trabecular meshwork. Electroretinography and immunohistochemistry were used to evaluate RGC function and density. Oxidative, inflammatory and apoptotic markers were evaluated by Western blot analysis.

RESULTS

The present results support an optimal efficacy of niacin with citicoline at their best dosage in preventing RGC loss. In fact, about 50% of RGCs were spared from death leading to improved electroretinographic responses to flash and pattern stimulation. Upregulated levels of oxidative stress and inflammatory markers were also consistently reduced by almost 50% after niacin with citicoline thus providing a significant strength to the validity of their combination.

CONCLUSION

Niacin combined with citicoline is highly effective in restoring RGC physiology but its therapeutic potential needs to be further explored. In fact, the translation of the present compound to humans is limited by several factors including the mouse modeling, the higher doses of the supplements that are necessary to demonstrate their efficacy over a short follow up period and the scarce knowledge of their transport to the bloodstream and to the eventual target tissues in the eye.

摘要

引言

抗氧化膳食补充剂备受关注,已知其可降低患青光眼的风险或延缓其进展。其中,烟酸和胞磷胆碱通过作用于线粒体来保护视网膜神经节细胞(RGCs)免于退化,尽管作用水平不同。本研究利用一种成熟的实验性眼压(IOP)升高诱导的RGCs退化小鼠模型,来探究烟酸/胞磷胆碱的新型组合在应对IOP升高时,在保护RGCs健康方面是否比单一成分具有更好的疗效。

方法

通过前房注射甲基纤维素堵塞小梁网来诱导高眼压。采用视网膜电图和免疫组织化学方法评估RGC功能和密度。通过蛋白质印迹分析评估氧化、炎症和凋亡标志物。

结果

目前的结果支持烟酸与胞磷胆碱在最佳剂量时预防RGC丢失的最佳疗效。事实上,约50%的RGCs免于死亡,从而改善了视网膜电图对闪光和图形刺激的反应。烟酸与胞磷胆碱联合使用后,氧化应激和炎症标志物上调水平也一致降低了近50%,从而为其组合的有效性提供了显著的依据。

结论

烟酸与胞磷胆碱联合使用在恢复RGC生理功能方面非常有效,但其治疗潜力仍需进一步探索。事实上,将目前的化合物应用于人类受到多种因素的限制,包括小鼠模型、在短随访期内证明其疗效所需的更高剂量补充剂,以及对其向血液和眼部最终靶组织转运的了解不足。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c579/10508956/c4fd9763c1f7/fmed-10-1230941-g001.jpg

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