Epigenetic modifications such as DNA methylation, histone post-translational modifications, non-coding RNA are reversible, heritable alterations which are induced by environmental stimuli. Major risk factors of diabetes and diabetic complications including hyperglycemia, oxidative stress and advanced glycation end products, can lead to abnormal epigenetic modifications in retinal vascular endothelial cells and retinal pigment epithelium cells. Epigenetic mechanisms are involved in the pathogenesis of macular edema and neovascularization of diabetic retinopathy (DR), as well as diabetic metabolic memory. The heritable nature of epigenetic marks also playsakey role in familial diabetes mellitus. Further elucidation of epigenetic mechanisms in DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
ObjectiveTo observe the expression of vascular endothelial growth factor (VEGF) and aquaporin 4 (AQP4) in the inner limiting membrane (ILM) of diabetic retinopathy (DR) with macular edema, and analyze the correlation between VEGF and AQP4 expression. Methods A cross-sectional study. From September 2019 to September 2020, 38 eyes of 38 patients with DR and idiopathic macular hole (iMH) who underwent vitrectomy (PPV) combined with ILM stripping at the Hangzhou campus of The Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. Among them, there were 25 males and 13 females who aged 37-76 years old, average age was 59±10 years old; All eye included 15 right eyes and 23 left eyes. iMH and DR included 9 eyes in 9 cases and 29 eyes in 29 cases, respectively, and they were divided into iMH group and DR group. The DR group was divided into DME group and no DME group according to whether it was accompanied by diabetic macular edema (DME), with 14 eyes and 15 eyes respectively. After the stripped ILM tissue was fixed, immunofluorescence analysis was performed to obtain a picture of the fluorescence mode of AQP4 and VEGF, and the fluorescence intensity value of VEGF and AQP4 was measured by Image J software. The differences of VEGF and AQP4 immunofluorescence values in the specimens between groups were compared by one-way analysis of variance. The correlation between the fluorescence intensity of AQP4 and the fluorescence intensity of VEGF was analyzed by Pearson correlation analysis. Results The average fluorescence intensity values?of VEGF and AQP4 in ILM specimens of DME group, no DME group and iMH group were 38.96±7.53, 28.25±3.12, 30.07±4.84 and 49.07±8.73, 37.96±6.45, 38.08±5.04, respectively. The average fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DME group was significantly higher than that of the no DME group and iMH group, and the difference was statistically significant (F=13.977, 9.454; P＜0.05). The average fluorescence intensity values of VEGF and AQP4 on IML specimens in the DR group were 33.80±7.91, 43.76±9.44, respectively. The results of Pearson correlation analysis showed that the fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DR group was significantly positively correlated (r=0.597, P=0.003). ConclusionsThe expressions of VEGF and AQP4 in ILM of eyes with DR and DME are significantly increased compared with those without DME. The expression of VEGF and AQP4 in ILM of eyes with DR is positively correlated.
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and it is the main cause of vision loss in diabetic patients. Angiopoietin (Ang), a superfamily of secreted proteins, is a vascular growth factor that regulates the stability of vascular environment, participates in angiogenesis and repair, and lipid metabolism. It plays an important role in the development of DR and has become a new target for the treatment of diabetic retinopathy. With the in-depth study of Ang and the research and development of various drugs for Ang, it is expected to bring new ideas and strategies for the treatment of DR in the future.
Objective
To investigate the relationship between dyslipidemia and diabetic retinopathy in non-insulin-dependent diabetes mellitus（NIDDM） patients．
Methods
In 55 health controls，60 NIDDM patients with DR and 75 NIDDM patients without DR，the plasma total cholesterol（TC），triglycerides（TG），high-density lipoprotein（HDL）and HDL subfractions，fasting plasma glucose（FPG），fasting plasma insulin（FINS）and glycosylated hemogolbin（HbA 1C）were measured，and the plasma lowdensity lipoprotein （LDL） and very lowdensity lipoprotein（VLDL）were caculated．
Results
In NIDDM patients with DR，the TC，LDL，FPG，HbA 1C and duration of NIDDM were higher or longer than those in NIDDM patients without DR．Moreover，the TC，LDL，FPG、FINS、HbA 1C and dutation of NIDDM were increased or lengthened in NIDDM patients with proliferative DR as compared with those with backgroud DR．The correlation analysis showed the severity of DR was positively correlated with TC，LDL，HbA 1C and duration of NIDDM．
Conclusion
Dyslipidemia may play some role in the onset and development of DR．
(Chin J Ocul Fundus Dis,1998,14:21-23)
Objective
To expolre the factors which affect the size of diabetic,macular fobeal avascss scular zone(FAZ).
Methods
Making ten years of duration of diabetes a limit,79 nonproliferative and early proliferative diabetic patients were divided into 2 groups.Diabetic retinopathy severity level was diveided into 4 stages,and the macular edema was subdivided into focal、diffuse and cystoid according to fluorescein leakage of foveomacular region.All patients were measured FAZ with Heidelberg scanning laser fluoresceion angiography system and then compaired the size of FAZ of patients with different duration of diabetes、diabetic retinopathy severity level and macular edema status.The results were performed analysis of variance and t test.
ResultsThe study shown the size of FAZ was not directly related to the duration of diabetes(t=1.3854,Pgt;0.1);There were significant differences about the size of FAZ of patients with different diabetic retinopathy severity level(F=7.6251,P＜0.01)and macular edema status(F=5.4369,P＜0.01)．
Conclusion
The size of FAZ was significantly increased in diabetic patients.It was enlarged with the development of diabetic retinopathy severity level,but it was not related to duration of diabetes.
(Chin J Ocul Fundus Dis,2000,16:155-156)
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 the effect of interleukin (IL) 10 modified endothelial progenitor cells (EPC) in diabetic retinopathy (DR).
MethodsEPC cells were collected and cultivated from the bone marrow of rats and identified by immuno-fluorescence staining. EPC cells were infected with lentivirus (LV) of EPC-LV-IL10-GFP (EPC-LV-IL10-GFP group) or EPC-LV-NC-GFP (GFP group). EPC cells without lentivirus infection was the EPC group. Enzyme-linked immuno sorbent assay (ELISA) was used to measure the concentrations of tumor necrosis factor (TNF)-α, IL10, IL8 and vascular endothelial growth factor (VEGF) in the supernatant of these three groups. 168 male Wistar rats were divided into normal control group (28 rats), diabetes mellitus (DM) group (28 rats), DM-blank control group (56 rats) and DM-intervention group (56 rats). DM was introduced in the latter 3 groups by streptozotocin intravenous injection. Three months later, the rats in the DM-blank control group and DM-intervention group were injected with EPC-LV-NC-GFP or EPC-LV-IL10-GFP by tail vein, respectively. Immunohistochemistry was used to observe the GFP expression in rat retinas. The blood-retinal barrier breakdown was detected by Evans blue (EB) dye. The retinal histopathologic changes were observed by transmission electron microscope. The mRNA level of VEGF, matrix metallproteinases-9 (MMP-9), angiopoietin-1 (Ang-1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in retina were measured by reverse transcription-polymerase chain reaction (RT-PCR).
ResultsELISA showed that the levels of TNF-αand IL8 in the supernatant significantly decreased, while the levels of IL10 and VEGF increased (P < 0.05) in EPC-LV-IL10-GFP group. GFP expressed in the retina of blank control group and intervention group, mainly in the ganglion cell layer, inner nuclear layer and outer plexiform layer. The retinal blood vessel pathological change and EB permeability significantly decreased in intervention group compared with DM group (P < 0.05), and blank control group (P < 0.05). RT-PCR revealed that the mRNA level of VEGF, MMP-9 and Ang-1 significantly increased, and eNOS decreased in DM group compared to the normal control group (P < 0.05). The mRNA level of VEGF and iNOS decreased, eNOS increased while Ang-1 and MMP-9 had not changed in DM-blank control group and DM-intervention group compared with DM group (P < 0.05).
ConclusionsIL10 modified EPC can improve the inflammative microenvironment and suppressed the pathogenesis of DR. Furthermore, EPC transplantation can increase the number of EPC and exerted their effect.
ObjectiveTo observe and preliminarily discuss the distribution characteristics of the non-perfusion area (NP) of the retina in different stages of diabetic retinopathy (DR) and its changes with the progression of DR. MethodsA retrospective clinical study. From October 2018 to December 2020, 118 cases of 175 eyes of DR patients diagnosed in Eye Center of Renmin Hospital of Wuhan University were included in the study. Among them, there were 64 males with 93 eyes and 54 females with 82 eyes; the average age was 56.61±8.99 years old. There were 95 eyes of non-proliferative DR (NPDR), of which 25, 47, and 23 eyes were mild, moderate, and severe; 80 eyes were proliferative DR (PDR). Ultra-wide-angle fluorescein fundus angiography was performed with the British Optos 200Tx imaging system, and the fundus image was divided into posterior, middle, and distal parts with Image J software, and the ischemic index (ISI) was calculated. The difference of the retina in different DR staging groups and the difference of ISI were compared in the same area. The Kruskal-Wallis test was used to compare the ISI between the different DR staging groups and the Kruskal-Wallis one-way analysis of variance was used for the pairwise comparison between the groups. ResultsThe ISI of the posterior pole of the eyes in the moderate NPDR group, severe NPDR group, and PDR group were significantly greater than that in the distal periphery, and the difference was statistically significant (χ2=6.551, 3.540, 6.614; P=0.000, 0.002, 0.000). In severe NPDR group and PDR group, the ISI of the middle and peripheral parts of the eyes was significantly greater than that of the distal parts, and the difference was statistically significant (χ2=3.027, 3.429; P=0.015, 0.004). In the moderate NPDR group, there was no significant difference in ISI between the peripheral and distal parts of the eye (χ2=2.597, P=0.057). The ISI of the posterior pole of the eyes in the moderate NPDR group and the PDR group was significantly greater than that in the middle periphery, and the difference was statistically significant (χ2=3.955, 3.184; P=0.000, 0.009). In the severe NPDR group, there was no significant difference in ISI between the posterior pole and the middle periphery of the eye (χ2=0.514, P=1.000). Compared with the mild NPDR group and the moderate NPDR group, the ISI of the whole retina, posterior pole, middle and distal parts of the PDR group was larger, and the difference was statistically significant (χ2=－7.064, －6.349,－6.999, －5.869, －6.695, －6.723, －3.459, －4.098; P=0.000, 0.000, 0.000, 0.000, 0.000, 0.000, 0.003, 0.000). ConclusionThe NP of the eyes with different DR stages is mainly distributed in the posterior pole and the middle periphery. The higher the severity of DR, the greater the NP in the posterior and middle periphery.
The pathogenesis of diabetic retinopathy (DR) is complex and there are many related risk factors. It is related to the course of diabetes, blood glucose, blood pressure, and blood lipids, among which the course of disease and hyperglycemia are recognized main risk factors. In addition, other factors which include heredity, gender, age, obesity, pregnancy, insulin use, can also affect the occurrence and development of DR, but there is no unified conclusion about its correlation. A comprehensive understanding of the risk factors that affect DR can provide new ideas for the prevention, diagnosis, treatment, and intervention of DR.
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.
