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候选蛋白从预先退化的神经中发挥时间特异性的保护作用,可防止青光眼的视网膜神经节细胞死亡。

Candidate proteins from predegenerated nerve exert time-specific protection of retinal ganglion cells in glaucoma.

机构信息

Chair and Department of Physiology, School of Medicine in Katowice, Medical University of Silesia, Medykow 18, 40-752, Katowice, Poland.

Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Ceglana 35, 40-515, Katowice, Poland.

出版信息

Sci Rep. 2017 Nov 6;7(1):14540. doi: 10.1038/s41598-017-14860-5.

Abstract

Glaucoma is thought to be the main cause of severe visual impairment or permanent loss of vision. Current therapeutic strategies are not sufficient to protect against glaucoma. Thus, new therapies and potential novel therapeutic targets must be developed to achieve progress in the treatment of this insidious disease. This study was undertaken to verify whether the time of administration of an extract from predegenerated rat sciatic nerves as well as exposure time of this extract onto retinal ganglion cells (RGCs) influences the survival of RGCs in a rat glaucoma model. We have demonstrated that extract obtained from the predegenerated sciatic nerves protects RGCs in a rat glaucoma model. The neuroprotective effect depends mostly on the time of administration of the extract and less clearly on the time of exposure to the extract and is associated with stimulation of endogenous BDNF expression both in RGCs and glial cells. The 14 day following glaucoma induction represents a therapeutic window for effective treatment in a glaucoma model. Mass Spectrometry analysis demonstrated that metallothionein 2 (MT2) may be a key molecule responsible for neuroprotective effects on RGC survival.

摘要

青光眼被认为是导致严重视力损害或永久性失明的主要原因。目前的治疗策略不足以预防青光眼。因此,必须开发新的治疗方法和潜在的新治疗靶点,以在治疗这种隐匿性疾病方面取得进展。本研究旨在验证预先退化的大鼠坐骨神经提取物的给药时间以及该提取物对视网膜神经节细胞(RGC)的暴露时间是否会影响大鼠青光眼模型中 RGC 的存活。我们已经证明,从预先退化的坐骨神经中提取的物质可在大鼠青光眼模型中保护 RGC。神经保护作用主要取决于提取物的给药时间,而与提取物暴露时间的关系不太明确,并且与内源性 BDNF 表达的刺激有关,无论是在 RGC 还是神经胶质细胞中。青光眼诱导后 14 天是在青光眼模型中进行有效治疗的治疗窗口。质谱分析表明,金属硫蛋白 2(MT2)可能是负责 RGC 存活的神经保护作用的关键分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ac0/5673995/d0f2271edfc2/41598_2017_14860_Fig1_HTML.jpg

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