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.
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 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.
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.
Microvesicles (MVs) is small membrane vesicles released from different cell types under different conditions. Studies have shown that MVs may mediate vascular inflammation, angiogenesis, and other pathological processes. MVs may play an important role in the pathogenesis of diabetic retinopathy (DR) by mediating endothelial cell injury, thrombosis and neovascularization. The plasma MV level may be an effective parameter to monitor the development of DR. This article will summarize the research progress of the relationship between MVs and DR in recent years.
ObjectiveTo observe the changes in open probability and protein expression of large conductance Ca2+-activated K+ (BK) channel in retinal vascular smooth muscle cells (RVSMCs) of diabetic rats. MethodsStreptozotocin (STZ)-induced rat diabetic animal model was established by STZ injection intraperitoneally.RVSMCs were isolated by enzyme digestion. The BK currents in control and diabetic groups were recorded by patch clamp technique in single channel configuration. BK channel protein expression in control and diabetic group were measured by Western blot. ResultsCompared with control group, the NP0 of BK channels in diabetic group were significantly increased (t=4.260, P < 0.05). Compared with control group, there was no significant difference inα-subunit protein expression in diabetic group in RVSMCs (t=10.126, P > 0.05); however, β1-subunit protein expression was remarkably increased in diabetic group (t=5.146, P < 0.05). ConclusionThe NP0 of BK channels andβ1-subunit protein expression are increased in RVSMCs of diabetic rats.
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 investigate the relationship between subclinical hypothyroidism (SCH) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 792 patients of T2DM were enrolled in the study. There were 448 males and 344 females, with an average age of (54.13±13.06) years. The average duration of diabetes was (8.03±6.70) years. The patients were grouped according to the degree of DR and thyroid function. Among them, 483 patients (61.0%) were no DR, 240 patients (30.3%) were mild DR, 69 patients (8.7%) were severe DR. 725 patients (91.5%) were normal thyroid function, 67 patients (8.5%) were SCH. The prevalence of SCH among no DR group, mild DR group and severe DR group was compared. And the prevalence of DR between normal thyroid function group and SCH group was compared. Logistic regression analysis was used to estimate the association between SCH and DR. Results No significant differences among the three groups (no DR group, mild DR group, severe DR group) were found in the prevalence of SCH (χ2=1.823,P=0.402). There were no significant differences in the incidences of DR between normal thyroid function group and SCH group (χ2=1.618,P=0.239). Logistic regression analysis demonstrated that SCH was not significant associated with DR [mild DR: odds ratio (OR)=1.361, 95% confidence interval (CI)=0.773−2.399,P=0.286; severe DR:OR=1.326, 95%CI=0.520−3.384,P=0.555; DR:OR=1.353, 95%CI=0.798−2.294,P=0.261). Conclusion SCH is not significant associated with DR in patients with T2DM.
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 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.