She Xiangjun, Zhou Yifan, Liang Zhi, Wei Jin, Xie Bintao, Zhang Yun, Shen Lijun
School of Ophthalmology, Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
Department of Ophthalmology, Putuo Poeple's Hospital, Tongji University, Shanghai 200070, China.
Metabolites. 2022 Nov 7;12(11):1077. doi: 10.3390/metabo12111077.
Retinal detachment is a serious ocular disease leading to photoreceptor degeneration and vision loss. However, the mechanism of photoreceptor degeneration remains unclear. The aim of this study was to investigate the altered metabolism pathway and physiological changes after retinal detachment. Eight-week-old male SD rats were fed, and the model of retinal detachment was established by injecting hyaluronic acid into the retinal space. The rats were euthanized 3 days after RD, and the retinal tissues were sectioned for analysis. Untargeted lipid chromatography-mass spectrometry lipidomic was performed to analyze the metabolite changes. A total of 90 significant metabolites (34 in anionic and 56 in cationic models) were detected after retinal detachment. The main pathways were (1) histidine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; and (3) glycine, serine, and threonine metabolism. The key genes corresponding to each metabolic pathway were verified from the Gene Expression Omnibus (GEO) database of human retinal samples. The results indicated that the production of histamine by histidine decarboxylase from histidine reduced after RD (p < 0.05). Xanthine, hypoxanthine, guanine, and guanosine decreased after RD (p < 0.05). Decreased xanthine and hypoxanthine may reduce the antioxidant ability. The decreased guanosine could not provide enough sources for inosine monophosphate production. Tyrosine is an important neurotransmitter and was significantly reduced after RD (p < 0.05). Citrate was significantly reduced with the increase of ATP-citrate lyase enzyme (ACLY) (p < 0.05). We inferred that lipid oxidation might increase rather than lipid biogenesis. Thus, this study highlighted the main changes of metabolite and physiological process after RD. The results may provide important information for photoreceptor degeneration.
视网膜脱离是一种严重的眼部疾病,可导致光感受器退化和视力丧失。然而,光感受器退化的机制仍不清楚。本研究的目的是探讨视网膜脱离后代谢途径的改变和生理变化。对8周龄雄性SD大鼠进行饲养,通过向视网膜下腔注射透明质酸建立视网膜脱离模型。视网膜脱离3天后对大鼠实施安乐死,并将视网膜组织切片进行分析。采用非靶向脂质色谱-质谱脂质组学方法分析代谢物变化。视网膜脱离后共检测到90种显著代谢物(阴离子模型中34种,阳离子模型中56种)。主要途径为:(1)组氨酸代谢;(2)苯丙氨酸、酪氨酸和色氨酸生物合成;(3)甘氨酸、丝氨酸和苏氨酸代谢。从人类视网膜样本的基因表达综合数据库(GEO)中验证了与各代谢途径对应的关键基因。结果表明,视网膜脱离后组氨酸脱羧酶由组氨酸生成组胺的量减少(p<0.05)。视网膜脱离后黄嘌呤、次黄嘌呤、鸟嘌呤和鸟苷减少(p<0.05)。黄嘌呤和次黄嘌呤减少可能会降低抗氧化能力。鸟苷减少无法为肌苷单磷酸的产生提供足够的原料。酪氨酸是一种重要的神经递质,视网膜脱离后显著减少(p<0.05)。随着ATP-柠檬酸裂解酶(ACLY)的增加,柠檬酸显著减少(p<0.05)。我们推断脂质氧化可能增加而非脂质生物合成。因此,本研究突出了视网膜脱离后代谢物和生理过程的主要变化。这些结果可能为光感受器退化提供重要信息。