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 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)
To evaluate the tberapeutlc effect of diode laser photocoagulation trearment on eases of diabetic retinopathy with certain degree of refractive media opacity. METHODS: Diode laser photocoagulation treatment were given to 36 selected cases (40 eyes )of diabetic retinopathy who can not be treated with argon laser because of refractive media opacity, Before and after treatment,visual acuity and fundus were examined and fundus fluorescein angiography and retinal color photographp were taken. The follow-up period was 8~14 months (with an average of 11 months) RESULT:Visual acuity were improved or maintained in 29 eyes(about 73%)of the 34 eyes of proliferative diabetic retinopathy ,retinal new vessels partly or entirely regressed in 25 eyes(about 74%). CONCLUTION ;Tbe effect of diode laser treatment on patients with diabetic retinopatby with certain degree of lens/vitreous opacity is relatively safisfactory. （Chin J Ocul Fundus Dis,1996,12:111- 113）
Objective To investigate the early influences of laser photocoagulation on retinal function in diabetic retinopathy(DR)． Methods The multifocal electroretinograms (MERG) of 30 eyes with DR (phase Ⅲ～Ⅳ) were tested with visual evoked response image system IV b efore,and the 3rd day and the 7th day after laser photocoagulation． Results Three days after photocoagulation, the latency of N1 prolonged in the central macula 5deg; area and superionasal quadrant．Th e response densities of N1,P1 and N2 markedly reduced, and most significant changes occurred in the central macula 5deg; area and then in the central 10deg;area． There were also differences in the changes of the amplitude of N1 and P1 in diff erent quadrants ．The changes of visual acuity were positively related to the de crease of amplitudes of N1,P1 and N2 in the macula． Conclusion The reduction of response densities in MERG reveals functional damage in diabetic retina occurring early after photocoagulation．The functional damage in macula induced indirectly by photocoagulation may explain the reduction of visual acuity after panretinal photocoagulation in some degree． (Chin J Ocul Fundus Dis, 2001,17:181-183)
ObjectiveTo compare the consistency of artificial analysis and artificial intelligence analysis in the identification of fundus lesions in diabetic patients.MethodsA retrospective study. From May 2018 to May 2019, 1053 consecutive diabetic patients (2106 eyes) of the endocrinology department of the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, 888 patients were males and 165 were females. They were 20-70 years old, with an average age of 53 years old. All patients were performed fundus imaging on diabetic Inspection by useing Japanese Kowa non-mydriatic fundus cameras. The artificial intelligence analysis of Shanggong's ophthalmology cloud network screening platform automatically detected diabetic retinopathy (DR) such as exudation, bleeding, and microaneurysms, and automatically classifies the image detection results according to the DR international staging standard. Manual analysis was performed by two attending physicians and reviewed by the chief physician to ensure the accuracy of manual analysis. When differences appeared between the analysis results of the two analysis methods, the manual analysis results shall be used as the standard. Consistency rate were calculated and compared. Consistency rate = (number of eyes with the same diagnosis result/total number of effective eyes collected) × 100%. Kappa consistency test was performed on the results of manual analysis and artificial intelligence analysis, 0.0≤κ＜0.2 was a very poor degree of consistency, 0.2≤κ＜0.4 meant poor consistency, 0.4≤κ＜0.6 meant medium consistency, and 0.6≤κ＜1.0 meant good consistency.ResultsAmong the 2106 eyes, 64 eyes were excluded that cannot be identified by artificial intelligence due to serious illness, 2042 eyes were finally included in the analysis. The results of artificial analysis and artificial intelligence analysis were completely consistent with 1835 eyes, accounting for 89.86%. There were differences in analysis of 207 eyes, accounting for 10.14%. The main differences between the two are as follows: (1) Artificial intelligence analysis points Bleeding, oozing, and manual analysis of 96 eyes (96/2042, 4.70%); (2) Artificial intelligence analysis of drusen, and manual analysis of 71 eyes (71/2042, 3.48%); (3) Artificial intelligence analyzes normal or vitreous degeneration, while manual analysis of punctate exudation or hemorrhage or microaneurysms in 40 eyes (40/2042, 1.95%). The diagnostic rates for non-DR were 23.2% and 20.2%, respectively. The diagnostic rates for non-DR were 76.8% and 79.8%, respectively. The accuracy of artificial intelligence interpretation is 87.8%. The results of the Kappa consistency test showed that the diagnostic results of manual analysis and artificial intelligence analysis were moderately consistent (κ=0.576, P＜0.01).ConclusionsManual analysis and artificial intelligence analysis showed moderate consistency in the diagnosis of fundus lesions in diabetic patients. The accuracy of artificial intelligence interpretation is 87.8%.
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 the early influences of laser photocoagulation on macular retinal thickness in diabetic retinopathy(DR). Methods Optic coherence tomography examination was performed in 30 eyes with DR(phase Ⅲ~Ⅳ) before, and on the 3rd day and the 7th day after photocoagulation respectively. The thickness of neuroretina and pigment epithelium were measured in the areas of fovea macula and 750 μm from fovea macula. Results Three days after photocoagulation, significant thickening of neuroretina was observed in the fovea macula, which is positively related with age, fasting blood sugar and duration of DR. There was no significant changes in the thickness of pigment epithelium in macula and in the thickness of neuroretina 750 μm from fovea macula. Conclusion Significant thickening of neuroretina in fovea macula in DR early after photocoagulation reveals progressed macular edema induced by photocoagulation which is positively related with age, fasting blood sugar and duration of DR. (Chin J Ocul Fundus Dis, 2002, 18: 31-33)
ObjectivesTo investigate the expression of E-selectin of adhesive molecule in microvessels in rats′ retina with diabetic retinopathy (DR) at the early, middle, and late phase.MethodsNinety Sprague Dawley (SD) male rats were randomly divided into normal control group (6, 9, and 12 months subgroups with 10 rats in each subgroup) and streptozotocin (STZ) DR group (6, 9, 12 months subgroups with 20 rats in each subgroup). The DR model was set up by one-off celiac injection with STZ at a dose of 60 mg/kg. The rats were executed according to the different time points, and the eyeballs were removed and the digested stretched preparations of retinal microvessels were made. E-selectin of adhesive molecule in microvessels was revealed by EnVision immunohistochemical staining, and the expression of E-selectin in retinal microvessels and the morphological changes were analyzed and observed by Leica-Q550W computer image analytical equipment. The relativity between degree of impairment of DR and expression of E-selectin was detected.ResultsMorphological changes: hyperplasia of endotheliocytes and decreased pericytes were found in 6month DR group; irregularly arranged retinal capillary networks, obviously thickened basilar membrane, many aggregation and adhesion of leucocytes to capillary walls, large areas of acellular capillaries, and opoptosis of endotheliocytes and pericytes were found in 9-and 12-month DR group. Results of quantitative analysis: there was no expression of E-selectin in normal control group, while expression of E-selectin with different degree in each DR group was found. There was significance difference among DR subgroups (Plt;0.01), and the highest expression was found in 6-and 12-month DR group.ConclusionsThe expression of adhesive molecule in microvessels in rats' retina increases as the disease course of DR extends, and has positive correlation with the degree of impairment of microvessels in DR. (Chin J Ocul Fundus Dis, 2005,21:318-321)
Diabetic macular ischemia (DMI) is one of the manifestation of diabetic retinopathy (DR). It could be associated with diabetic macular edema (DME), which may affect the vision of DR patients. FFA is the gold standard for the diagnosis of DMI, but with the advent of OCT angiography, a more convenient and diversified method for the evaluation of DMI has been developed, which makes more and more researchers start to study DMI. Intravitreal injection of anti-VEGF has become the preferred treatment for DME. When treating with DME patients, ophthalmologists usually avoid DMI patients. But if intravitreal anti-VEGF should be the contradiction of DME is still unclear. To provide references to the research, this article summarized the risk factors, assessment methods and influence of DMI. This article also analyzed the existing studies, aiming to offer evidences to a more reasonable and effective treatment decision for DME individual.
Objective To observe the effect of high glucose on the expression of activating transcription factor 4 (ATF4) in cultured retinal Muuml;ller glia cells. Methods The retinal tissue of Sprague-Dawley (SD) rats was collected, and Muuml;ller cells were isolated and cultured. The glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) of Muuml;ller cells were identified by streptavidin-biotin-peroxidase complex. Cultured rat Muuml;ller cells were divided into control group (5.5 mmol/L glucose), group A (20 mmol/L glucose), group B (30 mmol/L glucose) and group C (40 mmol/L glucose). ATF4 protein expressions in Muuml;ller cells of four groups were measured by Western blot four days after cultured. Results GFAP and GS expressed in more than 95% of Muuml;ller cells. Over 95% of Muuml;ller cells of group A, B and C were positive for GFAP and GS. Western blots indicated that ATF4 protein in group A, B and C increased obviously compared with the control group (q=0.293, 0.754,0.484;P＜0.05). Conclusion High glucose can increase the expression of ATF4 protein and cause endoplasmic reticulum stress in retinal Muuml;ller glia cells in vitro.