Dyslipidemia plays an important role in the pathogenesis of diabetic retinopathy (DR).Apreliminary study found that low-density lipoprotein cholesterol, apolipoprotein (Apo)Band ApoB/ Apo A1 ratio were positively correlated with DR, while high-density lipoprotein cholesterol, Apo A1 was negatively correlated with DR and proliferative DR. Reducing the blood fats to be helpful to DR control. However, the mechanism of hyperlipidemia in the pathogenesis of DR, the reason of dyslipidemia in diabetic patients and the interaction between hyperglycemia and hyperlipidemia in DR are not clear yet. Moreover, there is no predictive indicators related to blood lipid for DR. Understanding the relationship between dyslipidemia and DR can provide definite evidence for fat-reducing therapy for DR control.
Objective To analyze the expression of apoptosis-related genes of retinal blood vessel in early diabetic rats by gene chip technology. Methods To make diabetic rat model by intraperitoneal injection of streptozotocin (STZ). On the 6th week after blood pressure increased, 10 rats were executed in Diabetic group and normal control group respectively. 20 retinal blood vessels were extracted and the RNA was isolated. The probe was made of alpha;-32 P-deoxyadenosine triphosphate (dATP)-labeled sample which hybridized 1176 nylon chips, and then analyzed by software. Three different expression genes were selected to verify by reverse transcription polymerase chain reaction (RT-PCR). Results On the 6th week, 136 （11.5％） genes were differentially expressed ［up-regulated genes were 90(7.6%), down-regulated genes were 46(3.9%)］in diabetic group. These genes involved into different groups according to their function. Especially in 72 apoptosis-related genes, 15 genes were differentially expressed. The up-regulated genes were some TNF receptor family members such as TNFRSF12, TRAIL, TNFRSF9, FADD；Bcl-2 family members such as bcl-w, bax, bak1 and AKT. The down-regulated genes were FAF1 which related to fas. Conclusions The expression of retinal vascular gene in early diabetic rats has been changed complicatedly. In particular, the multiple apoptosis-related genes have been changed in early diabetic, and most of them are at the upstream of apoptosis pathway. These findings indicate that the development of diabetic retinopathy is associated with multiple signaling pathways leading to apoptosis, while the alterations on the level of molecular biochemistry are still limited in apoptosis induction period. （Chin J Ocul Fundus Dis，2008，24：244-248）
O-linked N-acetylglucosamine (O-GlcNAc) glycosylation is an important form of post-translational protein modification, mainly intracellular. It is closely related to cellular signaling pathways, and is involved in signal transduction, gene transcription and other important biological processes. Studies have found that O-GlcNAc glycosylation is directly related with diabetic retinopathy (DR), further studies may help us to uncover the DR mechanism, and develop new strategies for the diagnosis and treatment of this disease.
ObjectiveTo observe RNA-Seq analysis of gene expression profiling in retinal vascular endothelial cells after anti-vascular endothecial growth factor (VEGF) treatment.MethodsRetinal vascular endothelial cells were cultured in vitro, and the logarithmic growth phase cells were used for experiments. The cells were divided into the control group and high glucose group. The cells of two groups were cultured for 5 hours with 5, 25 mmol/L glucose, respectively. And then, whole transcriptome sequencing approach was applied to the above two groups of cells through RNA-Seq. Now with biological big data obtained as a basis, to analyze the differentially expressed genes (DEGs). And through enrichment analysis to explain the differential functions of DEGs and their signal pathways.ResultsThe gene expression profiles of the two groups of cells were obtained. Through analysis, 449 DEGs were found, including 297 upregulated and 152 downregulated ones. The functions of DEGs were influenced by regulations over molecular biological process, cellular energy metabolism and protein synthesis, etc. Among these genes, ITGB1BP2, NCF1 and UNC5C were related to production of inflammation; AKR1C4, ATP1A3, CHST5, LCTL were related to energy metabolism of cells; DAB1 and PRSS55 were related to protein synthesis; SMAD9 and BMP4 were related to the metabolism of extracellular matrix. GO enrichment analysis showed that DEGs mainly act in three ways: regulating biological behavior, organizing cellular component and performing molecular function, which were mainly concentrated in the system generation of biological process part and regulation of multicellular organisms. Pathway enrichment analysis showed that gene expressions of the two cell groups were differentiated in transforming growth factor-β (TGF-β) signaling pathway, complement pathway and amino acid metabolism-related pathways have also been affected, such as tryptophan, serine and cyanide. Among them, leukocyte inhibitory factor 9 and bone morphogenetic protein 4 play a role through the TGF-β signaling pathway.ConclusionsHigh glucose affects the function of retinal vascular endothelial cells by destroying transmembrane conduction of retinal vascular endothelial cells, metabolism of extracellular matrix, and transcription and translation of proteins.
ObjectiveTo observe the serum vascular endothelial growth factor (VEGF), apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR).MethodsA total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study. Vision, slit lamp microscope, indirect ophthalmoscope and FFA examinations were performed on all the subjects. According to the results of the examinations combined with the DR clinical staging criteria, the patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group, with 72, 76 and 60 patients in each, respectively. The clinical data of each group were recorded, and the levels of fasting blood glucose (FPG), HbA1c, total cholesterol (TC), three acylglycerol (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), VEGF, apelin and HO-1 were detected in each group. The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF, apelin and HO-1 in predicting the occurrence of PDR. Correlation analysis of serum VEGF, Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis.ResultsThe level of VEGF (56.82±10.16 vs 91.74±22.83, 140.15±36.40, 195.28±42.26 pg/ml) and apelin (2.95±0.53 vs 4.68±0.74, 7.25±1.13, 10.16±1.35 ng/ml) in PDR group were significantly higher than those in NPDR, NDR and control groups (F=17.306, 21.814; P＜0.05). The level of HO-1 (50.37±10.14 vs 43.58±8.16, 30.25±6.28, 22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR, NDR and control groups (F=15.827, P＜0.05). The ROC curve analysis showed that the best cut-off values of serum VEGF, apelin and HO-1 were 162.50 pg/ml, 8.30 ng/ml, 27.13 mmol/L, and the three combined to predict PDR of AUC (95%CI) was 0.906 (0.849−0.962), and their sensitivity (90.3%) and specificity (83%) were better. The correlation analysis showed that the VEGF, apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382, 0.416, −0.36; P＜0.05), FPG (r=0.438, 0.460, −0.397; P＜0.05) and HbAlc (r=0.375, 0.478, −0.405; P＜0.05), and the serum VEGF were correlated with apelin and HO-1 (r=0.793, −0.594; P＜0.01).ConclusionElevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR, and the three combination helps predict the occurrence of PDR.
It is clear that genetic background contributes to the development and progression of diabetic retinopathy (DR). However, the identification of susceptibility loci through candidate gene approaches, linkage disequilibrium analysis of case-control data and genome wide association study is still in its infancy and faces many challenges due to the complexity of the disease itself. China has rich resources of clinical samples. In order to facilitate elucidating the susceptibility genes of DR in China, we look forward multi-disciplinary, multi-regional collaboration studies integrating novel technologies, such as proteomics, metabolomics and next-generation sequencing to analyze gene-gene and gene-environment interaction factors comprehensively.
Objective To investigate the relationship between diabetic retinopathy (DR) and coronary atherosclerosis (CAS) in type 2 diabetes patients and other risk factors of DR. Methods A total of 118 patients of type 2 diabetes with DR (DR group), 120 patients of type 2 diabetes without DR matched in age and sex (non-DR group), and 86 normal controls (control group) were enrolled in this study. The body mass index (BMI), blood pressure (BP), fasting blood-glucose (FPG), glycosylated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterin (LDL-C), creatinine, estimate glomerular filtration rate (eGFR) and urinary albumin excretion rate(UAER) in all the subjects were measured. Meanwhile, the incidence of CAS in the three groups was detected by 64slice multidetector computed tomography angiography (MDCTA). Assume concurrent DR as dependent variable, clinical indicators and laboratory parameters as independent variable, the risk factors were determined by Logistic regression analysis. In addition, CAS as dependent variable, DR as fixed factor, analysis of covariance was used to investigate the relationship between CAS and DR. Results The incidence of CAS in DR group was higher than that in nonDR group and control group, the differences were statistically significant (chi;2=26.9,35.5;P＜0.05). The results of Logistic regression analysis showed that systolic BP, BMI, CAS, myocardial infarction and UAER were key risk factors for DR ［odds ratio (OR)=1.02, 0.89, 4.50, 3.89, 1.34;P＜0.05］. There was a negative relationship between BMI and DR. The results of analysis of covariance showed that there was significant correlation between CAS and DR (OR=5.31, 95% confidence interval=2.62-10.60; P＜0.05). Conclusion CAS is independently associated with DR in type 2 diabetes patients. In addition, the other risk factors for DR include systolic BP, BMI, myocardial infarction and UAER.
ObjectiveTo investigate the role of apelin, glycosylated hemoglobin (HbA1c), cholesterol (TC), triglyceride (TG), High density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC) in the development and progress of diabetic retinopathy (DR). MethodsThe serum concentration of apelin, HbA1c, TC, TG, HDLC and LDLC were measured in 30 normal control subjects and 90 patients with type 2 diabetic mellitus, including 30 cases without DR (NDR), 30 with non-proliferative DR (NPDR), 30 with proliferative DR (PDR). These data were analyzed by SPSS for windows 13.0. ResultsThe serum concentration of apelin, HbA1c, TC, HDLC, LDLC were significantly higher in NDR, NPDR, PDR group than those in control group (F=403.06, 5.45, 4.27, 201.56, 4.90;P < 0.05). The serum concentration of TG has no significantly difference (F=2.19, P > 0.05). The serum concentration of apelin, HbA1c, TC, LDLC were significantly higher in NDR, NPDR, PDR group than those in control group (t=0.30, 0.58, 0.79;P < 0.05), the serum concentration of HDLC were significantly lower than those in control group(t=0.79, P < 0.01). There were significantly positive correlation between the progression of DR and the serum concentration of apelin, HbA1c, TC, LDLC(r=0.962, 0.562, 0.935;P < 0.05). There were significantly negative correlation between the progression of DR and the serum concentration of HDLC(r=-0.753, P < 0.01). There were correlation between apelin and HbA1c, LDLC and HDLC(r=0.956, 0.741, -0.691;P < 0.01). ConclusionOur data demonstrated that serum apelin levels increased significantly in patients with diabetic retinopathy, and are closely related to blood sugar, blood lipid metabolic abnormalities.
Objective To determine the association of -429T/C and G1704T polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy (PDR). Methods Case-control study. From the Beijing Desheng Diabetic Eye Study cohort of 1467 patients with type 2 diabetes mellitus (T2DM),atotal of 97 patients with PDR and 105 diabetic patients without retinopathy (DWR, duration of diabetes 15 years) were included for this study. Questionnaires were collected and general ophthalmologic examinations were performed. Biochemical analysis was conducted. DNA was extracted from peripheral venous blood. The -429T/C and G1704T single nucleotide polymorphisms were detected by the means of PCR-restrication fragment length polymorphisms. Results The frequency distribution of -429T/C in DWR group was 81.0% in TT, 16.1% in TC, 2.9% in CC. The frequency distribution of -429T/C in PDR group was 77.3% in TT, 20.6% in TC, 2.1% in CC. There was no significant statistical difference between the two groups (χ2=0.40, P > 0.05). Frequency of the -429T/C minor alleleCin the DWR and PDR group were 11.0% and 12.4%, respectively, with no significant statistical difference between the two groups (χ2=0.20，P > 0.05). The frequency distribution of G1704T in DWR group was 66.7% in GG, 29.5% in GT, 3.8% in TT. The frequency distribution of G1704T in PDR group was 78.4% in GG, 21.6% in GT. There was no significant statistical difference between the two groups (χ2=3.44, P > 0.05). Frequency of the G1704T minor alleleTin the DWR and PDR group were 18.6% and 10.8%, respectively, in which significant difference was found within the two groups (χ2=4.79, OR=1.88，95%CI: 1.06 - 3.33, P > 0.05). Conclusions G1704T polymorphism is associated with PDR presence and 1704G allele may increase the risk of PDR.
ObjectiveTo assess the association of vascular endothelial growth factor (VEGF) gene-460C/T and-634C/G polymorphism with diabetic retinopathy (DR) among patients in Asia and European by meta-analysis. MethodsA systematic search of electronic databases (PubMed, Cochrane Library, EMBASE, VIP, Wanfang technological, CNKI, etc.) was carried out until Jun, 2014. Case-control studies on the relationship between genetic polymorphism of VEGF-460C/T and VEGF-634C/G with diabetic retinopathy were included in this analysis. The data were quantitatively analyzed by RevMan 5.0 software after assessing the quality of included studies. The pooled odds ratios (OR) and their corresponding 95% confidence intervals (CI) were used to assess the strength of the association. ResultsVEGF-460C/T (7 studies:899 cases and 786 controls) and VEGF-634C/G (10 studies:1615 cases and 1861 controls) were inclued in this meta-analysis. Significant association was found for-460C/T polymorphism in Aisa (C versus T:OR=1.52, 95%CI was, Z=3.72, P=0.0002; CC versus CT+TT:OR=1.61, 95%CI was[1.22, 1.90], Z=3.05, P=0.002; TT versus CT+CC:OR=0.64, 95%CI was[1.19, 2.19], Z=2.07, P=0.04), and VEGF-634CC gene type was associated with DR in European (OR=1.56, 95%CI[1.08, 2.25], Z=2.37, P=0.02). No significant publication bias was found. ConclusionsThe meta-analysis demonstrated that DR was associated with VEGF-460C/T polymorphism in Asia, and C alleles and CC gene type was the risk polymorphism; VEGF-634C/G polymorphism was not associated with DR, but its CC genotype maybe the risk factor in European. Further case-control studies based on larger sample size are still needed, especially for-634C/G polymorphism.