Basis And Clinical Research Of Diabetic Retinal Microangiopathy

Chapter 1 Evaluation of outer retinal tubulations in diabetic macular edema with retinal microangiopathy underwent anti-VEGF treatmentAim:To investigate the incidence and subsequent changes of outer retinal tubulations(ORTs)in diabetic macular edema(DME)with retinal microangiopathy underwent anti-vascular endothelial growth factor(VEGF)therapy,and to assess the possibility of ORT as a biomarker of DME severity or respones to anti-VEGF therapy.Methods:This retrospective and descriptive study included a total of.228 patients(435 eyes)with DME and treated with intravitreal anti-VEGF agents between March 2016 and January 2018.Patients were divided into 2 groups according to the presence of ORTs.The best corrected visual acuity(BCVA)was observed in both groups.High-resolution SD-OCT images acquired by vertical and horizontal scans and over consecutive visits were analyzed.The evolution of ORT over time,type of fluid,subfoveal photoreceptor integrity and changes of central retinal thickness(CRT)on OCT imaging was also assessed.Results:ORTs were identified in 108 eyes of 435 eyes with an overall incidence rate of 24.83%at baseline.ORTs were prone to locate adjacent to the lesions of exudation and/or cystoid edema and possibly situated in outer nuclear layer(ONL),outer plexiform layer(OPL)and/or inner nuclear layer(INL)in eyes with DME.The formation process of ORT led to focal downward displacement of OPL and INL toward RPE near the lesion.During the follow up,45 eyes had steady ORTs and 63 eyes had dynamic variants in ORTs,including disappearance,reappearance,collapse,diminution,and enlargement.There arc higher proportion of closed ORTs and fewer proportion of fonning ORTs in eyes with steady ORTs,which shows a statistically significance when compared with eyes with variant ORTs(P =0.006,P =0.017 respectively).The eyes without ORTs had significantly better mean final BCVA and more mean BCVA change than those eyes with ORTs in DME patients after anti-VEGF therapy.(P=0.023,P =0.009 respectively).The disauption of subfoveal photoreceptor integrity in eyes with ORTs was more serious than that in eyes without ORTs(P =0.013).The proportion of stable vision in eyes with ORTs was significantly higher than that in eyes without ORTs,showing statistical significance(P=0.016).ORTs were associated with worse visual prognosis due to damage of the subfoveal photoreceptor integrity.Conclusion:ORTs have a high incidence and changes over time in DME with anti-VEGF treatment and may be located at various retinal layers.Persistent ORT can be as a negative biomarker of outcome of DME.Chapter 2 Integrated analysis of microRNA expression profiles reveals the mechanism of action of KeLuoXin(?)for the treatment of diabetic retinal microangiopathyAim:The aim of this study was to investigate the potential effect of KeLuoXin(KLX)on expression of microribonucleic acids(miRNAs)of db/db mouse models with type 2 diabetic mellitius(T2DM)and provide theoretical basis for the therapeutic effect of KLX in diabetic retinal microangiopathy.Methods:Twenty-four db/db mice with T2DM were divided into four groups:780 mg/kg KLX,1560 mg/kg KLX,3120 mg/kg KLX and model control group,6 mice in each group.Six DB/+ mice in the fifth group were served as normal control group.Fundus fluorescein angiography and electroretinogram were performed 20 weeks after administration.High throughput sequencing was used for sequencing miRNAs and bioinformatics is used for analyse the miRNA-Seq data.Quantitative real-time polymerase chain reaction(qRT-PCR)was selected confirmed the expression levels of twenty miRNAs that were differentially expressed.Results:The differential expression analysis identified 64 miRNAs that were differentially expressed from T2DM model group to KLX-treatment group,miR-451a,-30b-5p,-374-5p,-690,-3470a,-136-3p,-29c-3p,-15a-5p and-18le-5p showed a gradual increase in expression in KLX-treatment db/db mice,and whereas miR-203-3p,-744-5p,-677-3p and-1981-5p.Epidermal growth factor receptor(ErbB)and transforming growth factor-β(TGF-p),sphingolipid signaling pathway and sphingolipid metabolism attributing to progression of diabetic retinopathy(DR)were also potentially regulated by KLX.Conclusion:In conclusion,our findings suggest that KLX may exert the retinal protection in T2DM by targeting miRNAs and regulating niRNAs-mediated signaling pathways downstream.