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.
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 compare the clinical results of yellow micro-pulse laser and traditional laser grid (MLG) photocoagulation for diabetic macular edema (DME). Methods Seventy-eight patients (106 eyes) with DME diagnosed by fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) were enrolled in this study. The patients were divided into micro-pulse group (39 patients, 51 eyes) and MLG group (39 patients, 55 eyes). The patients of micropulse group underwent 577 nm yellow micro-pulse laser therapy, while the patients of MLG group underwent continuous wavelength laser photocoagulation with a 561 nm yellow green laser. All the patients were examined documenting corrected visual acuity, macular retinal thickness (CMT) and mean sensitivity within macular 10 deg; examination before and after treatment. Six months after treatment was considered as the judgment time for the therapeutic effects. The mean corrected visual acuity, CMT and MS were comparatively analyzed. Results Six months after treatment, the mean corrected visual acuity of micropulse group and MLG group were 0.45plusmn;0.20 and 0.42plusmn;0.20, which increased significantly compared to those before treatment (t=3.404,2.316; P＜0.05). The difference of mean corrected visual acuity between before and after treatment of micro-pulse group and MLG group were 0.08plusmn;0.02 and 0.06plusmn;0.03, the difference was statistically significant between two groups (t=0.532, P＞0.05). The mean CMT of micropulse group and MLG group were (323.94plusmn;68.30) and (355.85plusmn;115.88) mu;m, which decreased significantly compared to those before treatment (t=4.028, 2.039; P＜0.05). The difference of mean CMT between before and after treatment of micro-pulse group and MLG group were (55.12plusmn;13.68) and (22.25plusmn;10.92) mu;m. The difference was not statistically significant between two groups (t=1.891,P＞0.05). The mean MS of micro-pulse group and MLG group were (6.63plusmn;2.65) and (4.53plusmn;1.81) dB. The mean MS of micro-pulse group increased significantly compared to that before treatment(t=3.335,P＜0.05). The mean MS of MLG group decreased significantly compared to that before treatment (t=3.589,P＜0.05). The difference of mean MS between before and after treatment of micro-pulse group and MLG group were (1.10plusmn;0.33) and (-0.91plusmn;0.25) dB.The difference was statistically significant between groups (t=4.872，P＜0.05). Conclusions In the treatment of DME, yellow micro-pulse laser therapy and MLG can improve visual acuity, and reduce CMT. In addition, yellow micro-pulse laser therapy can improve the MS, but MLG reduces MS.
The pathogenesis of diabetic retinopathy is complicated. The vast network of multiple factors including unifying mechanism, inflammatory reaction, neuron degeneration and metabolic memory of glucose, and the four established pathogenic molecular pathways are hotspots of mechanism research for diabetic retinopathy. Nevertheless, these researches may be only one corner of the ldquo;icebergrdquo; of DR mechanism, and we still face enormous challenges in DR mechanism research. Collaboration with multiple disciplines to study the relationship between DR and diabetes and other systemic diseases, search novel therapy targets may increase the result in an unexpected windfall for DR basic research.
Objective To observe the subfoveal choroidal thickness (SFCT) in eyes of patients with diabetic macular edema (DME). Methods Twenty patients (32 eyes) with DME were enrolled in this crosssectional observational study. The patients included 12 males and eight females, with a mean age of (47.3plusmn;10.2) years. All the patients were examined documenting best corrected visual acuity (BCVA), spectraldomain optical coherence tomography (OCT) and ophthalmological examination. According to OCT DME morphology, samples are divided into diffuse macular edema, cystoid macular edema, serous retinal detachment and hard exudate groups. The SFCT was measured by a Cirrus HD-OCT with enhanced depth imaging (EDI) and was compared with the average SFCT (286.84plusmn;28.80) mu;m of same age group. Correlation between SFCT and age, diopter, diabetic duration, fasting blood glucose, BCVA and central retinal thickness were analyzed by Pearson Analysis. SFCT of different DME types were analyzed by ANOVA Analysis. Results The mean SFCT of 32 eyes was (223.81plusmn;43.74) mu;m (ranging from 120.50 to 361.50 mu;m), which was lower by 63.03 mu;m (95% confidence interval, -78.80 to -47.26 mu;m, P＜0.01) from normal SFCT. SFCT was independent of age (r=0.124), diopter (r=0.277), diabetic duration (r=0.286), fasting blood glucose (r=0.408), BCVA (r=0.087), and central retinal thickness (r=0.036). There was no significant difference of SFCT between different DME types (F=0.042，P＞0.05). Conclusion SFCT is thinner in eyes with DME as compared to normal eyes of the same age.
Objective To observe the oxidative damage of mtDNA, apoptosis and expression of adhesion molecules in retinal capillary cells of diabetic rat with different disease courses. Methods One hundred Sprague-Dawley rats were randomly divided into the control group and the experimental group. The rats of experimental group were induced with streptozotocin (STZ) injection creating a diabetic model. Then they were divided into DR1m, DR2m DR3m group according to disease courses. The rats of control group were divided into NR1m, NR2m, NR3m group. Rat retinal capillaries were prepared, and then the contents of undamaged mtDNA were examined by Southern blot combined with Fpg. The expression of cyclooxygenase (COX)-1 encoded by mtDNA and transcription factors A (mtTFA) mRNA were detected by real-time quantitative polymerase chain reaction (RT-PCR). Apoptosis and expression of intercellular adhesion molecule-1 (ICAM-1) were detected by terminal dUT nick endlabeling (TUNEL) immuno-fluorescence and immunohistochemistry respectively. Results The contents of undamaged mtDNA in rats of DR1m, DR2m, DR3m were less than those of NR1m、NR2m、NR3m. The contents of undamaged mtDNA in diabetic rats decreased with the increase of disease courses. In addition, the mRNA levels of COX-1 and mtTFA were downregulated in diabetic rats. The positive cells of TUNEL and ICAM-1TUNEL and ICAM-1 in diabetic rats increased with the increase of disease courses. Conclusion With the increase of disease courses, mtDNA damage and apoptotic cells are increased, while the expression of mRNA encoded by mtDNA and ICAM-1 decreased in retinal capillary cells in diabetic rats.
Objective To investigate the relationship of macular microstructure and visual prognosis of micro-invasive vitrectomy for diabetic vitreous hemorrhage. Methods Fifty-three patients (53 eyes) with diabetic vitreous hemorrhage who underwent microinvasive vitrectomy were enrolled in this retrospective study. The preoperative and postoperative best-corrected visual acuities (BCVA) were recorded. The central foveal thicknesses (CFT) were measured after surgery by spectral domainoptical coherence tomography (SD-OCT). The median follow-up time was (12.81plusmn;8.22) months, ranging from six to 36 months. According to the results of SD-OCT at last follow-up time, macular edema (ME), epiretinal membrane (ERM), interrupted inside and outside section (IS/OS) and interrupted external limiting membrane (ELM) were macular abnormalities were observed. The preoperative and postoperative BCVA of different macular abnormalities were comparatively analyzed. The correlation between BCVA and macular microstructure were analyzed. Results The CFT was ranged from 103.00 mu;m to 498.00 mu;m,with the mean of（251.12plusmn;90.23） mu;m. Macular abnormalities were observed in 37 eyes (69.8%), and normal macula in 16 eyes (30.2%). Among 37 eyes with macular abnormalities, there were 20 eyes (37.7%) with ME, 12 eyes (22.6%) with ERM, 33 eyes (62.3%) with interrupted IS/OS, and 20 eyes (37.7%) with interrupted ELM. The BCVA of ME eyes decreased significantly than that in nonME eyes （t=-2.09，P＜0.05). The difference of BCVA in ERM and nonERM eyes was not statistically significant (t=-1.10,P＞0.05). The BCVA of interrupted IS/OS eyes decreased significantly more than that in continuous IS/OS eyes （t=-4.33,P＜0.05). The BCVA of interrupted ELM eyes decreased significantly more than that in continuous ELM eyes (t=-2.58, P＜0.05). The postoperative BCVA correlated positively with integrity of the IS/OS junction, CFT, and whether ME or not (r=7.65, 8.21, 4.99; P＜0.05), but insignificantly associated with integrity of the ELM and whether ERM or not (r=0.01, 0.82; P＞0.05). Conclusion The final visual acuity of patients with diabetic vitreous hemorrhage after micro-invasive vitrectomy is related to the CFT，the status of IS/OS junction, whether ME or not, but not related to integrity of the ELM or whether ERM or not.
Objective To observe the effect of resveratrol on retinal vasculopathy in diabetic rats. Methods Forty-five Sprague-Dawley male rats were randomly divided into the resveratrol group, treatment control group and the normal control group, 15 rats in each group. Diabetic rat models were induced with streptozotocin injection in resveratrol group and treatment control group. The same volume of sterile saline solution was injected into the rats of the normal control group. The rats of resveratrol group and treatment control group were feed with highfat diet. The rats of resveratrol group received oral gavage of resveratrol (75 mg/kg) twice a day for four months. The same volume of sterile saline solution was given by gavage in rats of treatment control group twice a day for four months. 2 ml femoral vein blood and 50 mu;l aqueous fluid of anterior chamber of the eye from rats of three groups were collected to detect fasting blood glucose, aqueous fluid glucose, cholesterol and triglyceride. The retinal vascular permeability was test by labeling with evans blue. Whole retina was isolated to detect the pericyte number. Total protein was extracted from retina to test the level of vascular endothelial growth factor (VEGF). Results The fasting blood glucose, aqueous fluid glucose, cholesterol and triglyceride in treatment control group were higher than those in normal control group, also higher than those in resveratrol group except cholesterol. The differences among the three groups were statistically significant (F=152.809, 65.230, 3.861, 15.059; P＜0.05). The retinal vascular permeability in treatment control group was higher than that in normal control group, while it in resveratrol group was lower than that in treatment control group. The differences among the three groups was statistically significant (F=11.626,P＜0.05). The pericyte number in treatment control group decreased as compared to normal control group, while it in resveratrol group increased as compared to treatment control group. The differences among the three groups was statistically significant (F=43.284, P＜0.05). The VEGF expression in treatment control group increased as compared to normal control group, while it in resveratrol group decreased as compared to treatment control group. The differences among the three groups was statistically significant (F=14.017, P＜0.05). Conclusion Resveratrol can improve abnormal retinal vasculopathy structure and function, down-regulated level of fasting blood glucose, aqueous fluid glucose, triglyceride and VEGF may be the mechanism.
Objective To observe the effects of dual targets intervention on the expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in diabetic rat retina. Methods Forty-eight Sprague -Dawley rats were randomly divided into control group (CON1 group) and diabetes mellitus group (DM group). The rats of DM group were induced with streptozotocin injection creating a diabetic model. Retinas were obtained at eight, 10, 12 weeks after DM induction from both groups. CTGF and VEGF mRNA levels were examined by realtime reverse transcriptionpolymerase chain reaction (RT-PCR). Based on the results of above experiments, 60 rats with same conditions were selected. Fifty rats were induced with streptozotocin injection creating a diabetic model, and 10 rats comprised the control group (CON2 group). Then the 50 diabetic rats were randomly divided into ranibizumab and CTGF shRNA dual targets intervention group, ranibizumab singletarget intervention group, CTGF shRNA singletarget intervention group and nonintervention group. Retinas were obtained at one week after intervention from all the groups. CTGF and VEGF mRNA levels were examined by RT-PCR. Results The levels of CTGF mRNA were significantly higher in DM group than that in CON1 group at the 8th weeks after DM induction, and this upregulation was maintained through the 12th week (t=-2.49, -2.67, -2.42;P＜0.05). There was no difference on VEGF mRNA levels between DM group and CON1 group at the 8th weeks after DM induction(t=-0.443,P=0.669). VEGF mRNA levels of DM group started to be significantly elevated over those in the CON1 group at the 10th week, and remained to be higher at the 12th week (t=-2.35, -2.57;P＜0.05). The VEGF mRNA of ranibizumab single-target intervention group was significantly lower than that in non-intervention group (t=-3.44,P=0.014), which was similar to CON2 group (t=-1.37,P＞0.05); however, the CTGF mRNA level was significantly increased as compared to the nonintervention group (t=2.48,P＜0.05). In the CTGF shRNA single-target intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=0.23, -2.92;P＜0.05). In the ranibizumab and CTGF shRNA dual targets intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=-6.09, -5.11;P＜0.001), which was similar to CON2 group (t=-1.16, 1.139; P＞0.05). Conclusions Both CTGF and VEGF gene expression are up-regulated in early diabetic rat retina, and the level of CTGF increased earlier than VEGF. Ranibizumab combined with CTGF shRNA could simultaneously reduce the level of CTGF and VEGF mRNA in diabetic rat retina.
Objective To study the relationship between central retinal thickness and retinal vascular filling state of patients with non-proliferative diabetic retinopathy (NPDR). Methods A total of 248 diabetic patients without retinopathy or with NPDR in the hospital were enrolled in the study. Only the right eye of these patients were examined by optical coherence tomography (OCT), fundus fluorescein angiography (FFA), color Doppler flow imaging (CDFI). Patients with central retinal edema, hemorrhage and exudation were excluded from this study. Central retinal thickness was measured by OCT at the points of 1 mm, 1 to 3 mm, and 3 to 6 mm from the fovea. The patients were divided into retinal thickness normal, thinning and thickening groups according to their central retinal thickness. The normal range of central retinal thickness was defined as 216.4-304.9 μm in this study. The arm retinal circulation time and retinal arterial phase and venous phase (A-V) fluorescence filling time were recorded by FFA examination. The peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI) of ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) were measured by CDFI examination. The retinal fundus vascular filling state and ocular hemodynamic indexes were compared between different groups. Results The arm retinal circulation time of retinal thickness normal, thinning, thickening groups was (10.42±0.51), (10.36±0.64), (12.94±0.46) seconds respectively; the retinal A-V fluorescence filling time was (9.15±1.36), (6.36±1.15), (13.56±2.04) seconds. The difference of the arm retinal circulation time was statistically significant between the thickening and normal groups (t=1.93,P=0.04), and between the thickening and thinning groups (t=4.49,P=0.00). The retinal A-V fluorescence filling time was statistically significant between the thinning and normal groups (t=2.13,P=0.03), and between the thickening and normal groups (t=2.49,P=0.02), and between the thickening and thinning groups (t=5.38,P=0.00).The difference of PSV (t=3.290, -5.520, -4.900), PI (t=-4.310,-5.230, -4.390) and RI (t=4.970, 6.160, 5.990) of OA, CRA and PCA was statistically significant between the thickening and thinning groups (P＜0.05). Conclusion Central retinal thickness can affect the retinal vascular filling state of diabetic patients without retinopathy or with NPDR.