Plasma Metabolomics Study Of Wet Age-Related Macular Degeneration

Wet age-related macular degeneration(w AMD)is a type of age-related macular degeneration.This disease is Bruch’s membrane damage caused by vitreous verruca.It can induce choroidal capillaries to produce new blood vessels.It can damage Bruch’s membrane,retinal pigment epithelial cells and photoreceptor cells,and cause severe loss of central vision or severe loss of vision.The disease mainly occurs in old age,its pathogenesis is not completely clear,the treatment also needs to be improved.The pathogenesis of w AMD is not very clear,and its treatment needs to be improved.In this study,broad target metabonomics was used to screen and analyze the differential metabolites between w AMD and controls or between w AMD sub-types.Then we explored the impact of four differential metabolites on various aspects of two cell types,namely,human retinal pigment epithelial cells(HRPECs)and human retinal endothelial cells(HRECs).The purpose of this study is to explore the pathogenesis of w AMD and to provide new potential strategies for the treatment of w AMD.First,high performance liquid chromatographyand tandem mass spectrometry(LCMS/MS)platform combined with MWDB(metaware database)and KEGG(Kyoto Encyclopedia of genes and genomes)databases were used to detect metabolices in the plasma of 127 cases of w AMD(67 cases of choroidal neovascularization,CNV and 60 cases of polypoidal choroidal vasculopathy,PCV)and 50 cases of controls.A total of 545 metabolites were identified in these samples.Among them,17 metabolites were significantly different between the patients with w AMD and the controls.Comparing with the controls,28 and 18 differential metabolites were identified in CNV and PCV patients,respectively.The metabolites of hyodeoxycholic acid and L-tryptophan amide were significantly different between PCV and CNV.The genetic association of metabolites of w AMD was also studied.For complement factor H(CFH)and high temperature requirement factor A1(HTRA1),we identified six differential metabolites between GG and AA genotypes of CFH rs800292,five differential metabolites between GG and AA genotypes of HTRA1 rs10490924,and four differential metabolites between GG and GA genotypes of HTRA1 rs10490924.Among the 545 metabolites,24 were annoted as microbial-specific metabolites.Finally,the effects of four differential metabolites(cyclamic acid,hyodeoxycholic acid,L-Tryptophan amide and O-phosphorylethanolamine)on the pathogenicity of w AMD were studied in vitro by using HRPECs and HRECs.Among them,cyclamic acid significantly reduced the activity of HRPECs,inhibited the proliferation of HRPECs,increased the apoptosis rate and necrosis rate of HRPECs,and reduced the migration rates of HRECs.Hyodeoxycholic acid significantly inhibited the activity,proliferation,apoptosis and necrosis of HRPECs,as well as the tubule formation of HRECs.Ltryptophan amide had no significant effect on the activity of HRPECs,but had different effects on the apoptosis,necrosis and proliferation of HRPECs,and increased the number of tubes and migration rates of HRPECs.The activity,proliferation,and necrosis of HRPECs were not significantly impacted by O-phosphorylethanolamine,but the tube formation and migration functions of HRECs were appreciably inhibited.