Studies On The Effects Of Long Non-Coding RNA MALAT1 On Diabetic Retinal Neurodegeneration

Purpose:To observe the effect of inhibiting lncRNA MALAT1 on diabetic retinal neurodegeneration.Methods:Thirty-six 8-week-old C57BL/6 mice were randomly divided into normal control,diabetic control,diabetic scrambled siRNA and diabetic MALAT1-siRNA groups.After diabetic induction with streptozocin intraperitoneally-injection,the diabetic MALAT1-siRNA group was intravitreally injected with 1μL 20μmol/L MALAT1-siRNA,and the diabetic scrambled siRNA group was injected with the same amount of scrambled siRNA.Electroretinography was performed to examine photoreceptor functions 16 weeks after diabetes induction.MALAT1 and TNFαexpression were detected via RT-PCR.Cone morphological changes were examined using immunofluorescence.Rod morphological changes were examined by determining outer nuclear layer thickness.Results:We found that retinal MALAT1 and TNFαexpression were upregulated in the diabetic control group,while MALAT1 expression in the diabetic MALAT1-siRNA group was decreased by 91.48% compared to diabetic control group.The expression of TNFα on the MALAT1 siRNA group is lower than the diabetes control and scrambled-siRNA group,the difference was statistically significant(P < 0.0125).The diabetic control and diabetic MALAT1-siRNA groups showed lower a-wave and b-wave amplitudes than did the normal control group in scotopic and photopic electroretinogram,while the diabetic MALAT1-siRNA group showed higher amplitudes than diabetic control group.Morphological examination revealed that outer nuclear layer thickness in the diabetic MALAT1-siRNA and diabetic control groups was lower than normal control group.However,outer nuclear layer thickness was greater in the diabetic MALAT1-siRNA group than diabetic control group.Moreover,the diabetic control group showed a sparser cone cell arrangement and shorter outer segment morphology than diabetic MALAT1-siRNA group.Conclusion:In summary,inhibiting retinal MALAT1 resulted in protective effects on the function and morphology of photoreceptors,thus alleviating diabetic retinal neurodegeneration.Purpose:Intricate signalling networks and transcriptional regulators translate pathogen recognition into defence responses.The aim of this study was to identify the weighted genes involved in diabetic retinopathy(DR)in different rodent models of diabetes.Methods:We performed a gene coexpression analysis of publicly available microarray data,namely,the GSE19122 dataset from the Gene Expression Omnibus(GEO)database.We conducted gene coexpression analysis on the microarray data to identify modules of functionally related coexpressed genes that are differentially expressed in different rodent models.We leveraged a richly curated expression dataset and used weighted gene coexpression network analysis(WGCNA)to construct an undirected network.We screened 30 genes in the most closely related module.A protein-protein interaction(PPI)network was constructed for the genes in the most related module using the Search Tool for the Retrieval of Interacting Genes(STRING).Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed for the 30 genes.Results:5 visual perception-related genes(Pde6g,Guca1 a,Rho,Sag and Prph2)were significantly upregulated.Based on the competing endogenous RNA(ce RNA)hypothesis,a link between the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1(MALAT1)and visual perception-related m RNAs was constructed using bioinformatics tools.Six potential micro RNAs(mi R-155-5p,mi R-1a-3p,mi R-122-5p,mi R-223-3p,mi R-125b-5p and mi R-124-3p)were also screened.Conclusions:MALAT1 might play important roles in DR by regulating Sag and Guca1 a through mi R-124-3p and Pde6 g through mi R-125b-5p.