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)
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.
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.
Objective To observe the serum betatrophin levels in patients with type 2 diabetes mellitus (T2DM) and to explore the role of betatrophin in the pathogenesis of diabetic retinopathy (DR). Methods A total of 59 patients with T2DM (DM group) and 14 healthy controls (NC group) were enrolled in the study. Vision, slit lamp microscope, indirect ophthalmoscope, fluorescein fundus angiography were performed on all the subjects. According to the results of the examination combined with the international DR clinical staging criteria, the patients were divided into no DR (Non-DR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group, with 30, 20 and 9 patients in each, respectively. The fasting blood glucose (FPG), insulin (FIN), C-peptide, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipid Protein (LDL-C) levels were detected. The level of betatrophin in serum was determined by enzyme-linked immunosorbent assay. The correlation between betatrophin and other indicators was analyzed by Spearman correlation. The influencing factors of PDR were analyzed by logistic regression. Results Compared with subjects in the NC group, the level of FPG (F=-4.316, P＜0.001), FIN (F=2.142, P=0.001), HbA1c (F=-5.726, P＜0.001), TC (t=3.609, P=0.010), LDL-C (t=0.000, P=0.003), and betatrophin (F=-2.263, P=0.024) were significantly increased and HDL-C level (F=-3.924, P＜0.001) was decreases in the DM group. The difference of TG level between two groups was not statistically significant (F= -1.422, P=0.155). Compared with the Non-DR group and the NPDR group, the serum C-peptide (F=7.818, P=0.020) and betatrophin levels (F=12.141, P=0.002) were significantly increased in the PDR group. Spearman correlation analysis showed that the levels of betatrophin in the DM group was positively correlated to TC (r=0.304, P=0.019). The serum levels of betatrophin was positively correlated to body mass index in the Non-DR group (r=0.513, P=0.004). Furthermore, in the PDR group, a significant positive correlation was observed between the serum betatrophin levels and diastolic blood pressure (r=0.685, P=0.042). Logistic regression analysis showed that the duration of diabetes, serum C-peptide and betatrophin levels were risk factors for PDR. After controlling for the duration and serum C-peptide, the PDR risk for betatrophin levels great than or equal to 1.0 ng/ml was 12 times as much as betatrophin levels less than 1.0 ng/ml in T2DM patients. Conclusions The serum betatrophin content of patients with T2DM is abnormal. Betatrophin may be involved in the occurrence and development of PDR.
Objective To observe the correlation between postmenopausal estrogen levels and diabetic retinopathy (DR) in women. Methods Thirty-nine menopause female patients with type 2 diabetes mellitus and 17 menopause subjects (control group) were enrolled in this study. Control subjects aged from 53 to 82 years, with the mean age of (69.80±8.32) years. Diabetes mellitus patients aged from 56 to 84 years, with the mean age of (70.50±8.27) years; diabetes duration ranged from 3 to 23 years, with the average course of diabetes (11.40±7.97) years. DR diagnosis was according to the results of fundus fluorescein angiography, and thus the 39 patients were divided into DR group (19 patients) and non-DR (NDR) group (20 patients). There was no significant difference in age and menopause duration between the three groups (t=0.347, 0.485;P＞0.05). There was significant difference in diabetes course (t=2.748,P＜0.05). Compared with NDR group, fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) were significantly increased (t=6.130, 5.322, 4.574, 2.426, 4.033), high density lipoprotein cholesterol (HDL-C) was significantly lower (t=3.917), the difference was statistically significant (P＜0.05). The level of estradiol (E2) was measured by radioimmunoassay. The differences of E2 levels between the three groups were compared. Logistic regression analysis was used to analyze the influencing factors of DR. Results The levels of E2 in control group, DR group and NDR group were (42.38±8.64), (21.49±9.81) and (32.72±10.51) pg/ml, respectively. The level of E2 in DR group was significantly lower than that in NDR group and control group (t=3.443, 10.110;P＜0.05). Logistic regression analysis showed that the duration of diabetes mellitus [coefficients =0.166, odds ratio (OR)=1.181,P= 0.016], FBG (coefficients=1.162,OR=4.014,P=0.001), TC (coefficients=3.212,OR=10.820,P=0.002), TG (coefficients=1.649,OR=5.203,P= 0.030) and LDL-C (coefficients=1.605,OR= 4.976,P=0.003) were the risk factors for DR; E2 (coefficients=−0.100,OR=0.904,P=0.004) and HDL-C (coefficients=−4.460,OR=0.012,P=0.002) were the protective factors for DR. Conclusion The estrogen level of postmenopausal women have a certain correlation with the development of DR, it may be one of the protective factor of DR.
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.
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.
Objective To measure the concentration of serum transthyretin (TTR) of patients with different stages of diabetic retinopathy (DR). Methods A total of 176 patients with diabetes mellitus were included in this study. There were 104 males and 72 females. The patients aged from 21 to 74 years, with the mean age of (56±11) years. The diabetes duration raged from 1 to 30 years, with the mean diabetes duration of (10±7) years. The HbA1C was 5.2%−14.1%, with the mean HbA1C of (8.6±2.0)%. According to the fundus examination, 58 patients had DR (33.0%), but the other 118 patients not (67.0%). For these DR patients, 10 patients were in stage Ⅰ (5.7%), 26 patients in stage Ⅱ (14.8%), 8 patients in stage Ⅲ (4.5%), and 14 patients in stage Ⅳ (8.0%). The concentration of serum TTR was measured by enzyme-linked immunosorbentassay kit. The differences in the concentration of serum TTR between different DR stages were compared.Bivariate analysis was used to analyze the influencing factors of TTR. Results The concentrations of serum TTR of the patients without DR or with DR of stage Ⅰ to Ⅳ were (224.96±65.47), (383.68±102.99), (247.44±63.21), (228.2±45.89), (189.34±70.12) mg/L, respectively. The difference between different DR stages was statistically significant (F=14.690,P＜0.001).Bivariate analysis showed that the concentration of TTR was correlation to DR (r=0.179,P=0.017). There was no correlation between the concentration of TTR and diabetes duration (r=−0.027,P=0.727), hypertension (r=0.018,P=0.810), hyperlipoidemia (r=0.101,P=0.182), and the use of insulin (r=−0.032,P=0.675). Conclusion The concentration of serum TTR was increased in early DR patients, and gradually decreased with the progression of DR. The concentration of TTR is correlated to DR.
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.