Metabolic alterations in the visual pathway of retinitis pigmentosa rats: A longitudinal multimodal magnetic resonance imaging study with histopathological validation
Metabolic alterations in the visual pathway of retinitis pigmentosa rats: A longitudinal multimodal magnetic resonance imaging study with histopathological validation
复制标题
视网膜色素变性大鼠视觉通路的代谢改变：纵向多模态 MRI 研究及组织病理学验证
DOI：
10.1002/nbm.4751
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发表时间：
2022-05-13
影响因子：
2.9
通讯作者：
Zhan，Yang
中科院分区：
文献类型：
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作者：
Duan，Fei;Xiao，Zebin;Zhan，Yang
由于色素性视网膜炎 (RP) 已被证明会引起整个视觉通路的退行性变化，因此迫切需要对 RP 引起的退行性变进行纵向评估，并确定成像方案以尽早检测这种退行性变。在本研究中，我们通过使用互补的无创磁共振成像技术，即质子磁共振波谱（1H-MRS）评估了RP转基因大鼠模型，以研究RP的代谢变化。我们的研究表明，与对照大鼠相比，皇家外科学院 (RCS) 大鼠视觉皮层中 N-乙酰天冬氨酸 (NAA)、谷氨酸 (Glu)、γ-氨基丁酸 (GABA) 和牛磺酸 (Tau) 的浓度和与肌酸 (Cr) 的比率降低，而肌醇 (Ins) 和胆碱 (Cho) 增加 (p< 0.05)。此外，随着RP的进展，NAA、Glu、GABA和Tau的浓度以及GABA/Cr和Tau/Cr的比值随着时间的推移显着降低，而Ins和Cho的浓度以及Ins/Cr的比值随着时间的推移显着增加（p< 0.05）。此外，在RCS大鼠中，NAA/Cr在出生后3至4个月显着下降（p<0.001），而Cho/Cr在出生后4至5个月显着增加（p=0.005）。同时，通过免疫组化染色可证实出生后5个月RCS大鼠的1H-MRS指标。总之，随着RP的进展，视觉皮层的代谢变化表明进行性重编程，神经元和轴突减少，并伴有胶质细胞增殖。
Because retinitis pigmentosa (RP) has been shown to cause degenerative changes in the entire visual pathway, there is an urgent need to perform longitudinal assessments of RP‐induced degeneration and identify imaging protocols to detect this degeneration as early as possible. In this study, we assessed a transgenic rat model of RP by using complementary noninvasive magnetic resonance imaging techniques, namely, proton magnetic resonance spectroscopy (1H‐MRS), to investigate the metabolic changes in RP. Our study demonstrated decreased concentrations and ratios to creatine (Cr) of N‐acetylaspartate (NAA), glutamate (Glu), γ‐aminobutyric acid (GABA), and taurine (Tau), whereas myo‐inositol (Ins) and choline (Cho) were increased in the visual cortex of Royal College of Surgeons (RCS) rats compared with control rats (p< 0.05). Furthermore, with the progression of RP, the concentrations of NAA, Glu, GABA, and Tau, and the ratios of GABA/Cr and Tau/Cr significantly decreased over time, whereas the concentrations of Ins and Cho and the ratio of Ins/Cr significantly increased over time (p< 0.05). In addition, in RCS rats, NAA/Cr decreased significantly from 3 to 4 months postnatal (p< 0.001), and Cho/Cr increased significantly from 4 to 5 months postnatal (p= 0.005). Meanwhile, the1H‐MRS indicators in 5‐month postnatal RCS rats could be confirmed by immunohistochemical staining. In conclusion, with the progression of RP, the metabolic alterations in the visual cortex indicated progressive reprogramming with the decrease of neurons and axons, accompanied by the proliferation of gliocytes.