Diabetic retinopathy is a serious complication of diabetes and is the leading cause of blindness in people with diabetes. At present, there are many views on the pathogenesis of diabetic retinopathy, including the changes of retinal microenvironment caused by high glucose, the formation of advanced glycation end products, oxidative stress injury, inflammatory reaction and angiogenesis factor. These mechanisms produce a common pathway that leads to retinal degeneration and microvascular injury in the retina. In recent years, cell regeneration therapy plays an increasingly important role in the process of repairing diseases. Different types of stem cells have neurological and vascular protection for the retina, but the focus of the target is different. It has been reported that stem cells can regulate the retinal microenvironment and protect the retinal nerve cells by paracrine production, and can also reduce immune damage through potential immunoregulation, and can also differentiate into damaged cells by regenerative function. Combined with the above characteristics, stem cells show the potential for the repair of diabetic retinopathy, this stem cell-based regenerative therapy for clinical application provides a pre-based evident. However, in the process of stem cell transplantation, homogeneity of stem cells, cell delivery, effective homing and transplantation to damaged tissue is still a problem of cell therapy.
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.
Purpose Researching the relared risk factors of diabetic retinopathy (DR) through the epidemiological investigation. Methods Basing on a population random sampling survey and screening in 6 areas and cities of Anhui,216 diabetics were screened and they were then investigated in detail by filling in forms,measuring blood pressure,ocular examination including ophthalmoscopy,and lab examination including fasting blood glucose (FBG),blood glucose 2 hours after meal,urine albumin excretion (UAE),serum triglyceride,and cholesterol. Results The resultant date revealed that the duration of diabetes,blood pressure FBG and UAE were associated significantly with DR (Plt;0.05),and serum triglyceride and cholesterol were associated not significantly with DR(Pgt;0.05). Conclusion Long duration of diabetes,hight FBG and hight blood pressure are the important risk factors of DR,and urine albumin might forebode the occurrence of DR. (中华眼底病杂志,1998,14:119-121)
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.
Objective To observe the genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy (PDR) in Chongqing Han population. Methods 400 type 2 diabetes (T2D) patients (case group) and 600 age- and sex-matched healthy controls (control group) were enrolled in this study. There were 8 PDR patients in case group. All the subjects were Han ethnic people. The immune-related representative SNP locus of C5 gene including rs2269067, rs7040033, rs7027797 were screened by linkage disequilibrium analysis. Locus rs1017119 was selected by TagSNP and was around the above three loci. Subjects′ peripheral venous blood was collected and DNA was extracted. Genotyping was examined by PCR-restriction fragment length polymorphism method. The level of C5 plasma protein was measured by enzyme-linked immunoabsorbent assay. Results The frequency of GG genotype of rs2269067 was significantly increased in PDR patients in cases group compared with controls (Pc=3.4×10-5, OR=1.87, 95%CI=1.43 - 2.44；P=3.1×10-6). There was no differences in frequency of G, CC and CG genotype of rs2269067 between two groups (P=1.4×10-4, 1.000, 1.0×10-6). There were no differences in frequency of G, CC, CG, GG genotype of rs7040033, rs1017119, and rs7027797 between two groups (P > 0.05). The production of C5 plasma protein was significantly increased in case group as compare with control group (P=0.0004). An increased production of C5 plasma protein was observed in rs2269067 GG genotype cases compared to CG or CC cases (P=0.003, 0.001). Conclusion C5 rs2269067 GG genotype may be associated with the PDR of T2D in Chongqing Han population.
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.
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.
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.
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.