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 determine the affected factors of intraorbital hemodynamic results in diabetic retinopathy (DR) and the risk factors related to the occurrence of DR. Methods Posterior ciliary artery (PCA), central retinal artery (CRA), central retinal vein (CRV), and vortex vein (VV) of 68 patients with DR were measured by color Doppler flow image (CDFI). Thirty-one hemodynamic parameters, including systolic velocity, diastolic velocity, mean velocity, resistive index, pulsatility index and accelerative velocity of ophthalmic artery (OA), and other variates (blood pressure, blood sugar, gender, age, duration of the disease, and so on) were collected and clustered in a principal components analys is following a forward, stepwise logistic regression on these components. Results Nine principal components were extracted from 37 original variates, reflecting the velocity of OA, velocity of PCA, resistance of OA, velocity of CRA,resistance of CRA, resistance of PCA, time-related factor, venous drainage factor and gender factor, respectively. In the result of logistic regression, resistance of OA, velocity of CRA, resistance of PCA, time-related factor, and venous drainage factor were the risk factors related to DR. Conclusion The first risk factor affecting DR is time, and intraorbital hemodynamic abnormity influencing the development of diabetic retinopathy may be the increase of resistance of OA, decrease of velocity of CRA, decrease of resistance of PCA, and increase of venous drainage. (Chin J Ocul Fundus Dis，2004，20：98-100)
OBJECTIVE:To investigate relationship between plasma endotbelin(ET)and serum angiotensin converting enzyme (ACE)levels and diabetic retinopathy (DR).
METHODS: Plasma ET and serum ACE levels were measured in 62 patients with diabetes mellitus(DM) and in 30 normal control subjects with radioimmunoassay and ultraviolet-spectrophotometry.
RESULTS:Plasma ET and serum ACE levels in patients with DR were significantly higher than in patients without DR (P＜0.01). Along with the progression of DR,plasma ET levels were significantly elevated and serum ACE levels were gradually elevated.
CONCLUSIONS :These findings suggest that increased plasma ET and serum ACE levels may be related to the development and progression of DR.
（Chin J Ocul Fundus Dis,1996,12: 177-179）
Purpose
To identify matrix metalloproteinase (MMP) in human vitreous samples of diabetic vitreoretinopathy (DR) and other ocular diseases (non-DR) and to probe the related factors of MMP expression．
Methods
Thirty-one diabetic and 17 non-diabetic vitreous samples (nine macular hole and eight epiretinal membrane patients) were examined． Samples were concentrated and subjected to substrate zymography to conduct a quantitative analysis of MMP-2,9 activity． The technology of Western blotting against anti-human MMP-2,9 was performed to identify MMP in vitreous samples．
Results
Vitreous samples both from DR patients and from non-DR patients showed a single band at the position of 72 kDa, correspondin g to MMP-2． Quantitative analysis revealed that diabetic vitreous showed higher MMP-2 activity than non-DR, although the difference was not significant.45.2% of DR patients showed MMP-9, but no expression in non-DR．Among DR samples, the positive ratio of MMP-9 in partial posterior vitreous detachment (PVD)(66．7%) was significantly higher than that of complete PVD (15．4%)． Western blotting study confirmed the expression of MMP-2 and MMP-9．
Conclusion
There is no obvious difference of MMP-2 activity between DR and non-DR． MMP-9 may be involved in the pathogenesis of diabetic vitreor etinopathy and the deterioration of proliferative change．
(Chin J Ocul Fundus Dis, 2001,17:195-197
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.
Objective
To investigate the early effects of intervention with tanakan on retinal function in diabetic retinopathy(DR) after laser photocoagulation.
Methods
Prospective random controlled study was performed on 60 Patients (60 eyes) from 23 to 69 years old with DR(phase Ⅲ～Ⅳ). The multifocal electroretinograms (MERG) were tested with VERIS Ⅳ before, the 3rd day and the 7th day after photocoagulation.
Results
No significant differences were found in the latencies and response densities of N1,P1 and N2 between the two groups before photocoagulation. Compared with that before photocoagulation, three days after photocoagulation the latencies in tanakan group had no significant change. The response densities of N1,P1 and N2 reduced and the changes were much smaller than that in control. Three days after photocoagulation, the response densities of P1 and N2 in the central macula 5°area were much higher and the latencies of P1 and N2 were significantly shorter than that in control group. There were no significant differences in the response densities in the 7th day and the differences in the latencies between two groups still existed.
Conclusion
Tanakan may be effective in preventing the retina from damage of retinal photocoagulation in some degree in DR.
(Chin J Ocul Fundus Dis, 2002, 18: 208-211)
Objective
To detect the difference of the light sensitivity in the central visual field between normal people and type Ⅱ diabetic patients without diabetic retinopathy, and evaluate the effect of perimetric examination in early diagnosis of diabetic retinopathy.
Methods
The light sensitivity at the 80 locations in the central field was measured by Dicon field analyzer (model TKS-4000) in 76 normal eyes of 44 normal volunteers aged from 45 to 72 years and 75 eyes of 40 type Ⅱ diabetic patients without retinopathy aged from 46 to 71 years.
Results
For the diabetic patients without diabetic retinopathy, the light sensitivity of locations decreased by 4-8 dB,and there were some decreased light sensitivity areas. The mean light sensitivity of three zones of the central field had significant reduction in the diabetic patients as compared with the control group(Plt;0.001).
Conclusion
The retinal neurosensory function of diabetic patients is damaged in some degrees before diabetic retinopathy occured, and no relationship is found between the decrease of retinal light sensitivity and localized blood-retinal barrier leakage. It is suggested that examination of central field with computerized perimetry has certain clinical significance in early diagnosis of diabetic retinopathy.
(Chin J Ocul Fundus Dis, 2002, 18: 218-220)
ObjectiveTo investigate the expression of miR-195 and the underlying molecular mechanisms of miR-195 regulating HMGB1 in diabetic retinopathy (DR).
MethodsExtract 5 ml venous blood from DR patients, diabetes mellitus (DM) patients and normal subjects, then extract and perificate plasma total RNA. MicroRNA array and real time polymerase chain reaction (RT-PCR) was used to screen out miRNAs which were expressed with significant differences in the serum of patients with DR. Bioinformatics was employed to predict the miR-195 related to high mobility group box 1 (HMGB1) regulation. Next, miR-195 was down-regulated or up-regulated in umbilical vein endothelial cells through transfection of miR-195 inhibitor and miR-29b mimics respectively.Then we analyzed expression of HMGB1 mRNA and protein by RT-PCR and Western blot.
ResultsMicroRNA array results showed the expression of miR-195 in DR group is decreased by 8.34 times and 11.47 times compared with DM group and the normal group. RT-PCR verification results conforms to the microRNA array results. Compared with the DM group (F=0.034, t=8.057) and the normal group (F=0.370, t=9.522), the expression of miR-195 in DR group were significantly reduced, the differences were statistically significant (P < 0.05). RT-PCR showed that the expression of HMGB1 mRNA was significantly decreased in up-regulation group, compared with blank (F=0.023, t=11.287) and negative control group (F=0.365, t=7.471), the difference was statistically significant (P < 0.05). The expression of HMGB1 mRNA was significantly increased in down-regulation group, compared with blank (F=0.053, t=10.871) and negative control group (F=0.492, t=6.883), the difference was statistically significant (P < 0.05). Western blot showed that the expression of HMGB1 protein was significantly decreased in up-regulation group, compared with blank (F=0.021, t=8.820) and negative control group (F=0.039, t=7.401), the difference was statistically significant (P < 0.05); and significantly increased in down-regulation group, compared with blank (F=0.186, t=10.092) and negative control group (F=0.017, t=12.923), the difference was statistically significant (P < 0.05).
ConclusionMiR-195 can inhibit the expression of HMGB1, reduce the inflammation and angiogenesis, thereby delaying or inhibiting the occurrence and development of DR.
ObjectiveTo investigate the expression of interleukin-18（IL-18）and signal transducers and activators of transcription 5（STAT5）in retina of 4-24-week-old diabetic rats, and explore the potential molecular mechanisms involved in diabetic retinopathy (DR).MethodsRetinal gene expression profile of healthy and 8-week-old diabetic rats was established with restriction fragment differential displaypolymerase chained reaction (RFDD-PCR), and the differences was analyzed by bioinformatics. IL-18 and STAT5 were filtrated as the candidate genes of DR. The expression of IL-18 and STAT5 in retina of diabetic rats with the age of 4, 8, and 24 weeks was observed by semi-quantitative reverse transcriptase-polymerase chain reaction（RT-PCR）.ResultsThe result of RFDD-PCR showed:expression of IL-18 was higher in healthy retina than that in diabetic one; expression of STAT5 was not found in healthy rats but in diabetic ones. The result of RT-PCR showed：compared with the normal, high expression of IL-18 was found in 4-week diabetic retina, reduced in 8-week one, and decreased to the lowest in 24-week one. The expression of STAT5 was not observed in healthy or 4week diabetic retina, but occurred in 8-week one, and increased in 24-week one. ConclusionThe expression of IL-18 and the activation of STAT5 may relate to the occurrance of DR. The expression of IL-18 doesn′t depend on the activation of STAT5. (Chin J Ocul Fundus Dis, 2005,21:258-260)
To observe the efficacy of intravitreal injection of conbercept (IVC) combined with panretinal laser photocoagulation (PRP) in the treatment of diabetic retinopathy (DR) combined with stage I and II neovascular glaucoma (NVG).MethodsA clinical case-control study. From October 2013 to March 2019, 50 eyes (50 patients) with DR and stage Ⅰ to Ⅱ NVG diagnosed in the Department of Ophthalmology, Peoples's Hospital of Xianghe were were included in the study. There were 27 eyes (27 males) and 23 eyes (23 females); all patients were monocular with the average age of 53.5±7.13 years old. Stage Ⅰ and Ⅱ NVG were 11 and 39 eyes, respectively. All patients underwent BCVA, intraocular pressure, and fundus angiography. The BCVA examination adopted the international standard visual acuity chart, which was converted to logMAR BCVA visual acuity in statistics. The patients were divided into the Conbercept+laser therapy (combination therapy) group and the laser therapy group by random number table, with 25 eyes. The age of the two groups of patients (t=0.058), gender composition ratio (χ2=0.081), logMAR BCVA (t=0.294), intraocular pressure (t=－0.070), the number of eyes with different grades of angle and iris neovascularization（χ2=1.683, 0.854）were compared, the difference was not statistically significant (P＞0.05). The changes of BCVA, intraocular pressure, iris neovascularization, and angular neovascularization were compared and observed between the two groups one week after the completion of PRP treatment, 1, 3, 6, and 9 months. Independent sample t test was used for continuous variables. Between the combination treatment group and the laser treatment group, at different time points within the two groups and the interaction of the two factors, a single-factor repeated analysis of variance was used.ResultsCompared with the results before treatment, the combined treatment group and laser treatment group had statistically significant differences in the number of angle and iris neovascularization, intraocular pressure and logMAR BCVA at different times after treatment in the combined treatment group and laser treatment group (F=124.211, 65.153, 69.249, 26.848; P＜0.001). After treatment, the combined treatment group was better than the laser treatment group in terms of the regression of eye angle and iris neovascularization, intraocular pressure and logMAR BCVA, and the difference was statistically significant (F=47.543, 25.051, 12.265, 9.994; P=0.001, 0.001, 0.001, 0.003). At different times after treatment, compared with the laser treatment group, the number of neovascularization in the iris and angle of the eye in the combined treatment group was less, the intraocular pressure was significantly decreased, and the BCVA was increased. The difference was statistically significant (P＜0.05).ConclusionThe efficacy of Kang IVC combined with PRP in the treatment of DR with stage Ⅰ and Ⅱ NVG is better than that of PRP alone.
