Nicotinamide-Rich Diet in DBA/2J Mice Preserves Retinal Ganglion Cell Metabolic Function as Assessed by PERG Adaptation to Flicker

Nicotinamide-Rich Diet in DBA/2J Mice Preserves Retinal Ganglion Cell Metabolic Function as Assessed by PERG Adaptation to Flicker
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DOI:
10.3390/nu12071910
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发表时间:
2020-07-01
期刊:
影响因子:
5.9
通讯作者:
Porciatti, Vittorio
Porciatti, Vittorio
中科院分区:
医学2区
文献类型:
--
作者:
Chou, Tsung-Han;Romano, Giovanni Luca;Porciatti, Vittorio

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闪烁的光线增加了视网膜内部的新陈代谢需求。闪烁可能会加重青光眼患者线粒体功能的缺陷,这将反映在视网膜神经节细胞(RGC)功能的敏感测试模式视网膜电信号(PERG)中。我们测试了闪烁是否改变了DBA/2J(D2)青光眼小鼠的PERG,以及富含维生素B3的饮食是否对闪烁效应起到了作用。D2小鼠分别饲喂标准饲料(对照组,n=10)和富含烟酰胺的饲料/水(NAM,每天2000 mg/kg)(处理组,n=10),观察3~12个月。以101赫兹(基线)或11赫兹(测试)的叠加闪烁(F-PERG)记录PERG,并评估基线测试的幅度差(适应性)。终点时,对平铺的视网膜进行免疫组织化学染色(RBPMS和mito-tracker)。3个月龄D2的F-PERG适应性为41%,与NAM饲养的D2相比,对照组D2的F-PERG适应能力随着年龄的增长而降低(Gee,p<0.01)。在终点,对照组D2的F-PERG适应性为0%,NAM喂养的D2为17.5%,同时RGC密度更高(2.4x),RGC胞体更大(2x),线粒体染色强度更高(3.75x)。F-PERG适应可能提供一种非侵入性工具来评估RGC在增加代谢需求时的自动调节,并测试饮食/药物治疗对视神经疾病的影响。
Flickering light increases metabolic demand in the inner retina. Flicker may exacerbate defective mitochondrial function in glaucoma, which will be reflected in the pattern electroretinogram (PERG), a sensitive test of retinal ganglion cell (RGC) function. We tested whether flicker altered the PERG of DBA/2J (D2) glaucomatous mice and whether vitamin B3-rich diet contributed to the flicker effect. D2 mice fed with either standard chow (control,n= 10) or chow/water enriched with nicotinamide (NAM, 2000 mg/kg per day) (treated,n= 10) were monitored from 3 to 12 months. The PERG was recorded with superimposed flicker (F-PERG) at either 101 Hz (baseline) or 11 Hz (test), and baseline-test amplitude difference (adaptation) evaluated. At endpoint, flat-mounted retinas were immunostained (RBPMS and mito-tracker). F-PERG adaptation was 41% in 3-month-old D2 and decreased with age more in control D2 than in NAM-fed D2 (GEE,p< 0.01). At the endpoint, F-PERG adaptation was 0% in control D2 and 17.5% in NAM-fed D2, together with higher RGC density (2.4x), larger RGC soma size (2x), and greater intensity of mitochondrial staining (3.75x). F-PERG adaptation may provide a non-invasive tool to assess RGC autoregulation in response to increased metabolic demand and test the effect of dietary/pharmacological treatments on optic nerve disorders.