TRNA And Metabolomics Analysis In Diabetes-related Eye Diseases

Purposes: To investigate the circulating t RNA-derived RNA Fragments(t RFs)and t RNA halves(ti RNAs)profile of patients with diabetes and/or diabetic retinopathy,and metabolism of aqueous humor of diabetic cataract patients,in aims of finding potential mechanisms and therapeutic targets of diabetes-related eye diseases.Methods:(1)Isolate the serum RNA of negative control group and diabetes group,employ t RF&ti RNA PCR Array after RNA pretreatment,and explore the t RNA-derived RNA Fragments(t RFs)and t RNA halves(ti RNAs)profile of patients with diabetes,then validate the results by q PCR in larger populations.(2)Extract the serum RNA of negative control group and diabetic retinopathy group,upload samples on t RF&ti RNA PCR Array after RNA pretreatment,and analyze the t RNAderived RNA Fragments(t RFs)and t RNA halves(ti RNAs)profile of patients with diabetic retinopathy,then validate the results by q PCR in larger populations.Synthesis the inhibitor of targeted t RFs and ti RNAs,study the influences of t RFs and ti RNAs,on proliferation of ARPE-19 cells and h RMEC cells under high glucose conditions.(3)Human aqueous humor of age-related cataract patients and diabetic cataract patients were collected during cataract surgery.All samples had undergone NMR spectra analysis for metabolism.In addition,potential pathways involved in were also investigated.Results(1)The t RF&ti RNA profile significantly changed in diabetic patients without retinopathy compared to control groups,by validating the results by q PCR in larger population,we found 3'ti R?080?Pro TGG,TRF327,and 3030 A decresed.(2)The t RF&ti RNA expression levels significantly changed in diabetic retinopathy patients group compared to control groups,then q PCR was applied to validate the results in larger population,TRF327 and 3030 A were found significantly incresed.And3030 A could influence the proliferation of ARPE-19 cells under high glucose condition(3)In aqueous humor of diabetic cataract patients,four metabolites(glucose increased;valine,lysine,tyrosine decreased) were significantly changed compared with age-related cataract group.Several pathways such as aminoacyl-t RNA biosynthesis were involved in the formation of diabetic cataract.Conclusions(1)The t RF&ti RNA profile significantly changed in serum of diabetes and diabetic retinopathy patients,and they could regulate the progression of diabetic retinopathy by influencing the outer barrier of retina.The t RF&ti RNA could become potential serum biomarkers and therapeutic targets of diabetes and/or diabetic retinopathy.(2)Amino acids metabolism play crucial roles in diabetic cataract formation,various signaling pathways were involved in.This work may shed new insights into mechanism of diabetic cataract and potential therapeutic targets.