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.
PURPOSE:To investigale the influence of orally administered aldose reduetace inhibitor(ARI) and myo-inositol (MI)for contents of gluecose,sorbitol and myo-inositol in experimental diabetic retinal tissue in rat.
METHODS :The STZ-induced diabetic rats were administered ARI or MI by oral. The glucose sorbitol and myo-inositol in retinal tissues were analysed by high performance liquid chromatography after experimental period of 6 montbs. RESULTS:It was found that the contents of glucose and sorhitol were increased and myo inosltol was decreased in diabetic group. In diabetes with ARI group.the content of sorbitol was increased although the glucose was in high level. In diabetes wilb MI group,the sorbitol accumulaled and coment of myo-inositol was close to the normal control group.
CONCLUSIONS:The ARI can effectively obstruct sorbitol accumulation in retina. MI increase myo-inositol level but fail to reduce sorbitol contenl of retina.
（Chin J Ocul Fundus Dis,1997,13: 75-77 ）
Objective To explore and evaluate the protective effects of soluble fms-like tyrosine kinase recptor-1(sFlt-1) gene 2-3 and 2-4 transcellular region on retinal vascular leakage and phosphatidyl inositol-3 kinase (PI3K)/Akt pathway under hypoxia and/or hyperglycemia. Methods The plasmids pcDNA3.1-EGFP/sFlt-1(2-3) and pcDNA3.1-EGFP/sFlt-1(2-4) were constructed.. Two of these plasmids with carboxy methylation glucan (CMD) magnetic particles were transfected into human umbilical vein endothelial cells (HUVEC), which were cultured under hypoxia and/or hyperglycemia. The blood retinal barrier was evaluated by Evans blue permeation (EBP). Then the expression of p-Akt mRNA and protein were detected by reverse transcriptionpolymerase chain reaction (RT-PCR) and Western blot separately. Results In the diabetic rabbits, The blood retinal barrier breakdown was detected by the retinal vascular leakage of EBP. The expression of p-Akt mRNA and protein in hypoxia and hyperglycemia groups were also obviously increased. These changes were largely prevented by transfection the plasmids pcDNA3.1-EGFP/sFlt-1(2-3) and pcDNA3.1-EGFP/sFlt-1(2-4) (P＜0.01 in both groups). Conclusion Both sFlt-1(2-3) and sFlt-1(2-4) can make the retinal blood vessels less leaky and may be beneficial in preventing vision loss from diabetic retinopathy.
ObjectiveTo investigate the expression and relation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in rats with diabetic retinopathy.MethodFifty-five Wistar rats were randomly divided into the control group (10 rats), and 1, 3, and 5-month-diabetes group (15 rats in each diabetes group), and the diabetic models were set up. The expressions of VEGF and bFGF were detected by situ hybridation and immunohistochemistry on retinal paraffin sections.ResultsThe results of situ hybridation showed that expression of bFGF was found in 3-month-deatbtes group with the percentage of 77.8%, and 88.9% in 5-month-deatbtes group; the positive expression of VEGF was not found in 3-month-deatbtes group but in 5-month-deatbtes group with the percentage of 66.7%. Immunohistochemistry indicated that the positive expression of bFGF started in 3-month-deatbtes group with the percentage of 55.6%, and 88.9% in 5-month-deatbtes group; the percentage of the expression of VEGF was 33.3% in 3-month-deatbtes group and 88.9% in 5-month-deatbtes group.ConclusionThe expression of VEGF occurs after the expression of bFGF in rats with DR.(Chin J Ocul Fundus Dis, 2005,21:37-40)
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.
OBJECTIVE:To investigate the value of psychophysical testing for the macular function in the diegnosis of diabetic retinopathy(DR).
METHODS:To compare the testing results of macular light sensitivity and pattern visual evoked potential(P-VEP)of 30 eyes of 15 normal person with
those of 82 eyes of 41 diabetic patients(27 eyes without DR,55 eyes with simple type DR ).
RESULTS:The macular light sensitivity of diabetic patients is much lower than that of normal Control group(plt;0.05). In the diabetic group, 62.19% is abnormal in macular light sensitivity, 69.51% in P-VEP.
CONCLUSION: Testing of macular light sensitivit y is helpful in finding of diabetic retinopathy and early deterioration of macular visual function in diabetics.
（Chin J Ocul Fundus Dis,1996,12: 223-224）
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.
ObjectiveTo observe the adhension and stracking of leukocyte in the capillary vessels, and investigate the relationship between leukocyte and microvascular morphologic changes in retinal microvesselsof rats with early diabetes.MethodsA total of 90 healthy adult male Wistar rats were randomly divided into control and diabetes (induced by Streptozotocin, STZ) groups with 45 rats in each group. The rats in the diabetic group were further divided into 3, 7, and 14 days groups with 5 rats in each group, and 30, 90, and 180 days groups with 10 rats in each group. The right eyes of rats in each group were prepared for retinal digest preparations. The expression of leukocyte common antigen (CD45) was detected by immunohistochemical staining.ResultsFew CD45 positive cells in the retinal capillaries were seen in the control group. The expression of CD45 was significantly increased in the retinal capillaries 3 days after diabetes induction, and reached a peak at the 14th day. Morphological changes including capillary telangiectasia, atresia, and irregularity of capillary caliber were found in the retinal capillaries of rats 90 days after diabetes induction. The changes were aggravated 180 days after diabetes induction.ConclusionLeukocyte adhesion occurs in the early stage of diabetic retinopathy (DR), and is the beginning of the microvascular pathological changes. Leukocyte adhesion may play an important role in the occurrence and development of DR as the foundation of microvascular morphological changes.(Chin J Ocul Fundus Dis, 2003,19:344-347)
Objective To observe the expression of p53, bcl-2 genes, vascular endothelial cell growth factor（VEGF）, basic fibroblast growth factor（bFGF）, insulin-like growth factor-I （IGF-I）, and the receptors of these factors of retinal vascular endothelial cells (VECs) of 1- to 20-week diabetic rats, and the relationship between the expressions and cell cycle arrest.Methods Retinal sections of diabetic rats induced by alloxan were immunohistochemically stained and observed by light microscopy (LM) and electron microscopy (EM). Dot blotting and Western blotting were used to determine the expression of mRNA, proteins of p53 and bcl-2. Results Under LM, immunohistochemical positive expression of p53 and bcl-2 were found on the vessels of ganglion cell layer and inner nuclear layer of retinae of 8- to 20-week diabetic rats; under EM, these substances were observed depositing in VECs. The retinal VECs also expressed VEGF, bFGF, IGF-I and their receptors. There was no positive expression of other cell types in these retinae, all cell types of retinae in control group, or all cells of retinae of diabetic rats with the course of disease of 1 to 6 weeks. The result of dot blotting revealed that retinal tissue of 20-week diabetic rat expressed p53 and bcl-2 mRNA, and the result of Western blotting revealed that they also expressed p53 and bcl-2 proteins. But retinal tissues of control group did not. Positive expression of bax was not found in the retinae in control group or 1- to 20-week diabetic rats. Conclusion p53, bcl-2 may introduce cell cycle arrest of VECs of retinae in 8- to 20-week diabetic rats. High glucose might stimulate the expression of VEGF, bFGF, IGF-I and their receptors, and the growth factors may keep VECs surviving by self-secretion. (Chin J Ocul Fundus Dis，2003，19：29-33)
Diabetic macular edema (DME) is one of the common causes of visual impairment. Anti-vascular endothelial growth factor (VEGF) has become the preferred therapy for DME because of significant visual improvement. Early and intensive anti-VEGF therapy combined with other individualized treatments are currently the main strategy for DME treatment. Considering the complexity of DME and limitations of anti-VEGF therapy, there are still many problems and difficulties in the treatment of DME. Optimizing treatment strategies, strengthening management of the clinical course and developing new drugs, could improve the efficacy and maintain the improvement of visual acuity and visual performance.
