Kidney-eye metabolomics in a mouse mode of oxygen-induced retinopathy correlates with those in retinopathy of prematurity

Abstract

Background：Retinopathy of prematurity (ROP) is one of the leading causes of babies’ visual impairment and blindness. There is no effective intervention with ROP so far, and thus a deeper understanding of oxygen-induced metabolism may offer novel potential therapeutic approaches to ROP. The aim of this study is to explore a correlation of oxygen-induced renal metabolism with those in eyes and blood from ROP patients or a mouse model of oxygen-induced retinopathy (OIR). Methods：At postnatal day 7 (P7), 30 healthy C57BL6/J mice were randomly selected and divided into two groups, an OIR group and a WT group. The R-OIR group (N = 8) and R-WT group (N = 8) were examined for renal untargeted metabolomics; Targeted metabolomics analysis was performed to detect vitreous in V-OIR group (N = 7) and V-WT group (N = 7). Network association analysis was performed with the above results and previous studies: retinal-targeted metabolomics of OIR and human blood-targeted metabolomics of ROP. Results：The levels of metabolites in the R-OIR group were slightly higher than those in the R-WT group, especially in lipids. However, nucleotides of the R-OIR group were lower than the R-WT group. There were 9 canonical signaling pathways enriched, in which the initiation and progression of pathologic retinal neovascularization were closely associated with purine metabolism, arginine biosynthesis, histidine metabolism, pantothenate and CoA biosynthesis, alanine, aspartate and glutamate metabolism; arginine and proline metabolism, tryptophan metabolism, beta-Alanine metabolism, and D-glutamine as well as D-glutamate metabolism. In addition, L-histidinol, Isoguanosine, guanosine, guanine, nicotyrine, quinoxaline-2-carboxylic acid, L-3-hydroxykynurenine, N-gamma-glutamyl-S-propylcysteine, alanine, adenosine diphosphate, and ribose were potential biomarkers of ROP. Conclusion：Shikimic acid and PC(14:1(9Z)/20:2(11Z,14Z)) are highly specific biomarkers of renal metabolomics of OIR. Arginine biosynthesis is the best common pathway of kidney-untargeted OIR metabolomics, vitreous-, and retina-targeted OIR metabolomics, and blood-targeted metabolomics of ROP, indicating that arginine biosynthesis is the common pathway of ROP and neonatal kidney injury.