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 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 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.
Diabetic retinopathy (DR) is one of the most common and serious complication of diabetes mellitus, which is the main cause of vision loss in adults. Biological clock genes produce circadian rhythms and control its operation, while the disorder of the expression causes the occurrence and development of a series of diseases. It has been demonstrated that biological clock genes might take effects in the development and progression of DR. On the one hand, circadian rhythm disorder-related behavior disrupts the circadian oscillation of clock genes, and the change in its expression level is prone to unbalanced regulation of glucose metabolism, ultimately increasing the risk of type 2 diabetes mellitus and DR pathogenesis. On the other hand, DR patients exhibit symptoms of circadian rhythm disorders, and it has been suggested that the clock genes may control the development and progression of DR by affecting a variety of retinal pathophysiological processes. Therefore, maintaining normal circadian rhythm can be used as a disease prevention strategy, and studying the molecular mechanism of clock genes in DR can provide new ideas for more comprehensive elaboration of the pathogenesis of DR and search for new therapeutic targets.
ObejctiveTo investigate the consistency and reproducibility of macular perfusion parameters in early diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA).MethodsA prospective cross-sectional observational study. Forty-six patients (46 eyes) diagnosed with mild nonproliferative DR were included in this study. There were 24 males and 22 females, with the mean age of 59.16±10.32 years. Two macular scan sizes of 3 mm×3 mm and 6 mm×6 mm were performed by the same operator, and the same test was performed by another operator. The superficial retinal layer (SRL) and deep retinal layer (DRL) in the foveal avascular zone (FAZ) and vessel density (VD) were quantified. The consistency of the two scan sizes and the reproducibility of the same scan size were also evaluated. The consistency was determined by the intraclass correlation coefficient (ICC). If the intraclass correlation coefficient (ICC)＞0.80, consistency was good; if 0.4≤ICC＜0.8, consistency was general; if ICC＜0.40, consistency was poor.ResultsIn the 3 mm×3 mm and 6 mm×6 mm scanning sizes, the mean results of the two examiners were calculated. The FAZ of SRL were 0.39±0.13 mm2 and 0.42±0.15 mm2, FAZ of DRL were 0.74±0.22 mm2 and 0.89±0.23 mm2. The VD of SRL were (32.23±2.86)% and (31.91±3.01)%, VD of DRL were (43.73±4.64)% and (45.12±5.49)%. The consistency analysis showed that the ICC of SRL-FAZ and DRL-FAZ were 0.920 and 0.812, respectively; the ICC of VD were 0.833 and 0.830, respectively. The consistency was good. The reproducibility analysis of different examiners in the same scan size was better in the consistency of SRL FAZ and VD.ConclusionOCTA in two scanning sizes to measure FAZ and VD of early DR has good consistency and reproducibility.
The exact pathophysiological mechanisms of diabetic retinopathy (DR) remain elusive. The inflammatory reaction, retinal vascular leakage and retinal neovascularization are main features of DR. Adiponectin (APN) is an endogenous biological active protein secreted by adipocytes. It can increase insulin sensitivity, regulate blood glucose and lipid metabolism, and has anti-inflammation and anti-neovascularization functions. It may be involved in the development of DR. This review summarized the studies on the association between APN and DR in recent years.
ObjectiveTo observe the expression of Toll-like receptor 4 (TLR4) and inflammatory cytokines, leucocytic density and permeability in retina of diabetic rat. MethodsA total of 106 Brown Norway rats were randomly divided into experimental group and control group with 53 rats in each group. Diabetic model was established in experimental group by intraperitoneal injection of streptozotocin, and control rats received intraperitoneal injection of an equal volume of citric acid-sodium citrate buffer. Four weeks later, the retinas were collected for further analysis. TLR4 RNA and protein expression were measured by quantitative polymerase chain reaction and Western blot. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemo-attractant protein-1 (MCP-1), were measured by enzyme-linked immunosorbent assay in rat retina homogenate. Leukocyte density in the retina was measured by acridine orange fundus angiography. The retinal permeability was evaluated by Evans blue (EB) staining. ResultsTLR4 expression was significantly increased in diabetic rats of experimental group compared with non-diabetic rats of control group (F=1.606, 0.789; P < 0.05). Inflammatory cytokines (TNF-α, IL-1β and MCP-1) were significantly increased in retina of diabetic rats of experimental group versus non-diabetic rat of control group (F=24.622, 5.758, 4.829; P < 0.05). The retinal leukocyte density was (6.2±0.5)×10-5, (2.2±0.3)×10-5 cells/pixel2 in experimental and control group respectively, the difference was statistically significant (F=2.025, P < 0.05). The amount of retinal EB leakage was (23.41±4.47), (13.22±3.59) ng/mg in experimental and control group respectively, the difference was statistically significant (F=21.08, P < 0.05). ConclusionTLR4 and inflammatory cytokines expression, leucocytic density and permeability increased significantly in retina of diabetic rat.
Objective To explore the effects of bone marrow mesenchymal stem cells (BMSCs) transfected with adenovirus hepatocyte growth factor (Ad-HGF) on wound repair in diabetic rats. Methods BMSCs from male Wistar rats were isolated by density gradient centrifugation, cultured, and transfected with Ad-HGF. The multi pl icity of infection was 100. Diabetic models were establ ished in 20 female Wistar rats by diets in high fat and sugar plus intraperitoneal injection ofstreptozotocin (30 mg/kg). Then 2 full-thickness skin wounds (approximately 1.5 cm in diameter) were made on the dorsum. The rats were randomly divided into 4 groups (n=5 rats). After wounding, the 0.3 mL suspensions of BMSCs (group A), Ad- HGF (group B), BMSCs transfected with Ad-HGF (group C), and PBS (group D) were injected directly into the derma of wounds. The transverse diameter and longitudinal diameter of wound were measured at 21 days after treatment. At 7 days and 28 days after treatment, HE staining was performed to evaluate wound heal ing. The contents of hydroxyprol ine and advanced glycosylation end products (AGEs) in the wounds were measured by enzyme l inked immunosorbent assay and fluorospectrophotometer, respectively, at 3, 7, 14, and 28 days after treatment. Results At 21 days after treatment, the wounds almost healed in group C, and the transverse diameter and longitudinal diameter were 0 and (0.110 ± 0.024) cm, respectively. But the wounds healed partially in groups A, B, and D, and the transverse diameter and longitudinal diameter were (0.470 ± 0.051) cm and (0.590 ± 0.041) cm, (0.390 ± 0.042) cm and (0.480 ± 0.032) cm, and (0.700 ± 0.068) cm and (0.820 ± 0.068) cm, respectively. There were significant differences in wound heal ing between group C and groups A, B, and D (P lt; 0.05). The wound heal ing time of group C [(20.5 ± 1.9) days] was significantly shorter (P lt; 0.05) than those of groups A, B, and D [(28.3 ± 1.9), (25.9 ± 2.3), and (36.6 ± 5.1) days]. At 7 days, the HE staining showed that evident epidermis transportation, collagen formation, and leukocytes infiltration were observed in group C. At 28 days, the HE staining showed that the epidermis in group C was significantly thinner and more regular than those in other groups, and the decreased collagen and many small vessels were observed in group C. The content of hydroxyprol ine in group C was higher than those in groups A, B, and D at 7 days and 14 days (P lt; 0.05). The contents of AGEs in group C was lower than those in groups A, B, and D at 14 days and 28 days (P lt; 0.05). Conclusion Transplantation of BMSCs transfected with Ad-HGF can accelerate the wounds repair in diabetic rats.
ObjectiveTo compare the outcomes of 23G and 25G plus (25G+) vitrectomy in treatment of proliferative diabetic retinopathy (PDR). MethodsThis is a prospective randomized study. Fifty-seven PDR patients (75 eyes) with symptoms requiring vitrectomy were randomly divided into 23G vitrectomy group (30 patients, 39 eyes) and 25G+ vitrectomy group (27 patients, 36 eyes). Visual acuity, intraocular pressures, ophthalmoscopy, B-scan ultrasound was examined before surgery. The follow-up period was 10.0 (23G group) and 8.5 months (25G+ group) respectively. Intraoperative complications, operation time, postoperative visual acuity, intraocular pressure, postoperative complications and postoperative ocular conditions were analyzed. ResultsThe mean surgical times were (53.35±7.42) minutes and (49.16±5.17) minutes in 23G and 25G+ group respectively, and the difference was significant (t=4.37, P < 0.05). Iatrogenic injuries occurred in 11 eyes (28.21%) and 5 (13.89%) eyes in 23G and 25G+ group respectively, and the difference was significant (χ2=4.93, P < 0.05). The postoperative visual acuity of 23G and 25G+ group were improved compared to before surgery (χ2=16.81, 18.29; P < 0.05). At last follow-up, there was 25 eyes and 24 eyes with visual acuity≥0.05 in 23G and 25G+ groups respectively, and the difference was not significant (χ2=0.13, P > 0.05). Hypotony was detected in 7 and 3 eyes at the third postoperative day in 23G and 25G+ group respectively, and the difference was significant (χ2=5.67, P < 0.05). Conclusion25G+ vitrectomy is a safe and effective treatment for PDR with shorter surgery time and fewer surgical complications.
Objective To investigate the alteration of protein kinase C (PKC) and endothelin system in early diabetic rats, and the effect of specific PKC inhibitor on the expression of retinal endothelin-1 (ET-1). Methods The rats model with streptozotocin(STZ)-induced diabetes were set up. The expression of retinal PKC was detected by enzyme-linked immunoabsorbent assay (ELISA). The expression of retinal ET-1, ET-3, ET-A and ET-B receptor mRNA was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The alteration of retinal ET-1 mRNA after intravitreal injection of PKC inhibitor GF109203X in diabetic rats was also observed. Results The activities of membranous PKC were significantly increased in 2-week diabetic rats compared with that in normal rats（t=3.296 , P=0.008）, while activities of cytosolic PKC were unchangeable（t=0.138, P=0.894）. The expression of retinal ET-1 mRNA was significantly increased（P=0.008）, while no change was found in expression of ET-3, ET-A and ET-B mRNA（P=0.918，P=0.889，P=0.500）. After intravitreal in jection of 10-5、10-6、10-7 mol/L PKC inhibitor GF109203X in diabetic rats, the expression of retinal ET-1 mRNA was decreased in a dose-dependent manner compared with the control rats. Conclusion Activation of PKC and increased expression of ET-1 could be found in the retina of early diabetic rats, and PKC inhibitor could inhibit the expression of retinal ET-1. (Chin J Ocul Fundus Dis，2004，20：168-171)