de la Barca Juan Manuel Chao, Huang Nuan-Ting, Jiao Haihan, Tessier Lydie, Gadras Cédric, Simard Gilles, Natoli Riccardo, Tcherkez Guillaume, Reynier Pascal, Valter Krisztina
PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, 49933 Angers, France.
Département de Biochimie et Génétique, Centre Hospitalier Universitaire, 4 rue Larrey, 49933 Angers cedex 9, France.
Metabolomics. 2017;13(3):22. doi: 10.1007/s11306-016-1156-9. Epub 2017 Jan 20.
Light is the primary stimulus for vision, but may also cause damage to the retina. Pre-exposing the retina to sub-lethal amount of light (or preconditioning) improves chances for retinal cells to survive acute damaging light stress.
This study aims at exploring the changes in retinal metabolome after mild light stress and identifying mechanisms that may be involved in preconditioning.
Retinas from 12 rats exposed to mild light stress (1000 lux × for 12 h) and 12 controls were collected one and seven days after light stress (LS). One retina was used for targeted metabolomics analysis using the Biocrates p180 kit while the fellow retina was used for histological and immunohistochemistry analysis.
Immunohistochemistry confirmed that in this experiment, a mild LS with retinal immune response and minimal photoreceptor loss occurred. Compared to controls, LS induced an increased concentration in phosphatidylcholines. The concentration in some amino acids and biogenic amines, particularly those related to the nitric oxide pathway (like asymmetric dimethylarginine (ADMA), arginine and citrulline) also increased 1 day after LS. 7 days after LS, the concentration in two sphingomyelins and phenylethylamine was found to be higher. We further found that in controls, retina metabolome was different between males and females: male retinas had an increased concentration in tyrosine, acetyl-ornithine, phosphatidylcholines and (acyl)-carnitines.
Besides retinal sexual metabolic dimorphism, this study shows that preconditioning is mostly associated with re-organisation of lipid metabolism and changes in amino acid composition, likely reflecting the involvement of arginine-dependent NO signalling.
光是视觉的主要刺激因素，但也可能对视网膜造成损伤。让视网膜预先暴露于亚致死量的光（即预处理）可提高视网膜细胞在急性损伤性光应激下存活的几率。
本研究旨在探索轻度光应激后视网膜代谢组的变化，并确定可能参与预处理的机制。
在轻度光应激（1000勒克斯×12小时）后1天和7天，收集12只接受轻度光应激大鼠和12只对照大鼠的视网膜。一只视网膜用于使用百泰克p180试剂盒进行靶向代谢组学分析，而另一只视网膜用于组织学和免疫组织化学分析。
免疫组织化学证实，在本实验中，发生了伴有视网膜免疫反应和最小光感受器损失的轻度光应激。与对照组相比，光应激导致磷脂酰胆碱浓度升高。一些氨基酸和生物胺的浓度，特别是那些与一氧化氮途径相关的（如不对称二甲基精氨酸（ADMA）、精氨酸和瓜氨酸）在光应激后1天也增加。光应激后7天，发现两种鞘磷脂和苯乙胺的浓度较高。我们还进一步发现，在对照组中，雄性和雌性的视网膜代谢组不同：雄性视网膜中酪氨酸、乙酰鸟氨酸、磷脂酰胆碱和（酰基）肉碱的浓度增加。
除了视网膜性代谢二态性外，本研究表明预处理主要与脂质代谢的重新组织和氨基酸组成的变化有关，这可能反映了精氨酸依赖性一氧化氮信号的参与。
