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.
Uric acid (UA) is the final product of human purine metabolism. As one of the main antioxidants in the body, it can scavenge oxidative radicals. Under the action of oxidative-antioxidant shuttle mechanism, the antioxidant activity of UA can be reversed, causing inflammation and oxidative stress of vascular endothelial cells. Hyperuricemia (HUA) is considered to be one of the major risk factors for diabetes and diabetic nephropathy. The study of HUA in diabetic retinopathy (DR) is also a hot topic. UA can cause retinal vascular sclerosis, and affect the occurrence and development of DR by promoting oxidative stress and inducing neovascularization.
Objective To explore the relationship between the classification of diabetic macular edema（DME）and the stages of the diabetic retinopathy (DR) , the diabetic duration and the visual loss.Methods Retrospectively analyzed the clinical data of fundus fluorescein angiography (FFA) and other related information of 1521 patients who were diagnosed as DR. Classified DR according to national standard of the diagnosis and classification of DR, and classified DME according to the standard made by the early treatment diabetic retinopathy study research group of United States. The occurrence of DME in DR in each stage and the relationships between DME and the disease course and the vision were analyzed.Results In 1521 patients, 791 eyes in 468 patients had DME ( 30.77%), including 361 eyes (45.64%) with focal DME and 430 eyes (54.36%) with diffuse DME. The occurrence of DME was 1.13% in I-stage DR, 7.84%in II-stage DR, 41.98% in III-stage DR, and 48.93% in IV-stage DR. Focal and diffuse DME usually occurred at the III and IV stage of DR respectively, with 178 eyes (22.51%) with focal macular edema at the III stage of DR, and 249 eyes (31.48%) with diffuse DME at the IV-stage of DR. Patients with DME were hardly found at the V and VI stage of DR because of retinal proliferation and vitreous hemorrhage or other complications which made the condition of macula region blurred. The visual acuity of diffuse DME was worse than focal DME. DME often occurred within 10 years in the diabetic duration, and its severity and incidence increased year by year.Conclusions DME is the main cause of visual impairment of DR. The incidence of DME increased as the course of the DR prolonged. Along with the development of retinopathy, the incidence of DME increased, and the severity of DME aggravated, but the development of DME and its classification can not be brought into definite correspondence or unification with the classification of DR, hence the typing of DME in another individual classification in DR is of course necessary. (Chin J Ocul Fundus Dis，2003，19：83-86)
ObjectiveTo summarize the effectiveness and experience of Wanger grade 3-5 diabetic foot treated with vacuum sealing drainage (VSD) combined with transverse tibial bone transport.MethodsBetween March 2015 and January 2018, 21 patients with refractory diabetic foot who failed conservative treatment were treated with VSD combined with transverse tibial bone transport. There were 15 males and 6 females, aged 55-88 years (mean, 65 years). The diabetes history was 8-15 years (mean, 12.2 years). The duration of diabetic foot ranged from 7 to 84 days (mean, 35.3 days). The size of diabetic foot ulcer before operation ranged from 2 cm×2 cm to 8 cm×5 cm. According to Wanger classification, 8 cases were rated as grade 3, 11 cases as grade 4, and 2 cases as grade 5. Among the 21 cases, angiography of lower extremity before operation was performed in 5 cases, CT angiography of lower extremity in 16 cases, all of which indicated that the arteries below the knee were narrowed to varying degrees and not completely blocked. Preoperative foot skin temperature was (29.28±0.77)℃, C-reactive protein was (38.03±31.23) mg/L, leukocyte count was (9.44±2.21)×109/L, and the visual analogue scale (VAS) score was 6.8±1.5, and ability of daily living (Barthel index) was 54.3±10.3.ResultsAfter operation, 2 patients with Wanger grade 4 and smoking history failed treatment and had an major amputation (amputation above ankle joint) at 30 days and 45 days after operation, respectively. One patient with Wanger grade 5 and chronic heart failure died of cardiac arrest at 60 days after operation. The remaining 18 patients were followed up 6-24 months (mean, 9.2 months). The external fixator was removed at 40-62 days after operation, with an average of 46 days. All the wounds healed, with a healing time of 50-120 days (mean, 62.5 days). The pain of 18 patients’ feet was relieved obviously, and there was no recurrence of ulcer in situ or other parts. There was no complication such as tibial fracture and ischemic necrosis of lower leg skin after operation. After ulcer healing, the foot skin temperature was (30.86±0.80)℃, C-reactive protein was (22.90±18.42) mg/L, VAS score was 2.4±1.2, and Barthel index was 77.3±4.6, all showing significant differences when compared with preoperative ones (P<0.05); the leukocyte count was (8.91±1.72)×109/L, showing no significant difference (t=1.090, P=0.291).ConclusionVSD combined with transverse tibial bone transport can effectively promote the healing of Wanger grade 3-5 diabetic foot wounds, but smokers, unstable blood glucose control, and chronic heart failure patients have the risk of failure.
Objective
To investigate the effects of advanced glycation endproducts (AGEs) on proliferation of pericytes of bovine retinal capillary vessels and expression of transforming growth factor beta;(TGF-beta;).
Methods
The proliferation of pericytes detected by methyl thiazolyl tetrazolium (MTT) colorimetric assay, cellular cycle of pericytes was analyzed by flow cytometry was used to analyze cell, and TGF-beta; protein expression of pericytes was observed by immunofluorescent staining.
Results
AGEs inhibited the proliferation of pericytes of bovine retinal capillary vessels, stopped the cellular cycle of pericytes in synthesis phase (S phase), increased the number of apoptotic cells obviously (Plt;0.01), and promoted the expression of TGF-beta; proteinof perycytes.
Conclusions
AGEs may promote the apoptosis of pericytes by inhibiting the proliferation of pericytes to lead the decrease of pericytes number, and may accelerate diabetic retinopathy by promoting the expression of TGF-beta; protein of pericytes.
(Chin J Ocul Fundus Dis, 2006, 22: 20-23)
Objective
To observe the influence of rAAV-mediated antisense vascular endothelial growth factor (rAAV-aVEGF165) on the expression of retinal VEGF in diabetic rats.
Methods
40 Sprague-Dawley rats induced diabetic rat model by intraperitoneal injection with streptozotocin (STZ). 32 rats were involved in study besides death and blood sugar recovery in experimental process, 16 spragud-Dawleg (SD) rats were received intravitreal injection with rAAV-aVEGF165 (1010 pfu) as experimental group, another group of Sprague-Dawleg (SD) rats were injected with phosphate buffered saline (PBS) as control group. One and five month after model establishment, the expression of retinal VEGF was evaluate by immunhistochemistry and Western blot; the retinal vasular was examined by transmission electron microscopy.
Results
On 1 month,the expression of retinal VEGF was lowest in each group. On 5 month, the expression of retinal VEGF was decreased in experimental group which compared to control, the difference are statistically significant （t=23.87,Plt;0.01）. The transmission electron microscopy results showed that retina has no obvious chages in experimental group, however,contral group showed fragmental thickening and splitting of basement membrane, swelling and deformation of endothelia cells,fingerlike prcess into the capillary cavity,and uneven distibution of heterochromatin in pericytes.
Conclusion
rAAV-aVEGF165 can reduce the expression of retinal VEGF thereby preventing occurrence and development of diabetic retinopathy. rAAV is an effective vectors of eye antisense gene.
（Chin J Ocul Fundus Dis，2008，24：255-258）
The pathogenesis of diabetic retinopathy (DR) is complex. Antisense non-coding RNA (ANRIL) in the INK4 locus in long-chain non-coding RNA (lncRNA) is closely related to cell proliferation, differentiation, and individual development. It plays an important role in the dysplasia of retinal vascular endothelial cells and is a new field in the study of the pathogenesis of DR. According to the researches at present, ANRIL may plays its role in the occurrence and development of DR through the signal pathway of nuclear factor-κB and ROS/polyadenylation diphosphate ribose polymerase, and interact with p300, miR-200b, and EZH2 to regulating the expression and function of VEGF. Specific blocking ANRIL and its related pathways may become a new target in the treatment of DR.
Objective To evaluate the efficacy and safety of prostaglandin E1 (PGE1) for diabetic peripheral neuropathy (DPN). Methods We searched the Cochrane Library, PubMed, EMbase, CNKI, VIP and handsearched Chinese Journal of Metabolism, Chinese Journal of Diabetes and New Chinese Medicine. Randomized controlled trials of clinical therapeutic studies on PGE1 for DPN were included. The quality of included studies was evaluated and Meta-analysis was performed. Results Thirty-one trials involving 2 497 participants were included. Meta-analysis indicated that PGE1 was more effective than Vitamin B, Placebo and other microcirculation improving drugs in improving symptoms and signs of DPN. The RR (95%CI) were ［RR=1.75, 95％CI (1.54, 2.00)］, ［RRpooled=1.57, 95％CI (1.42, 1.74)］and［RR=1.31, 95％CI (1.19, 1.45)］respectively. PGE1 was more effective than Vitamin B, Placebo and other microcirculation improving drugs in improving nerve conduction velocity (NCV) of DPN patients. For spontaneous pain and hypesthesia of DPN patients, Lipo-PGE1 was more effective compared with PGE1-CD and the RR (95%CI) was［RR=1.43, 95％CI (1.16, 1.76)］. Slight adverse effects were reported in 16 studies. Conclusion Based on this review, PGE1 is effective for DPN. However, the evidence is not b enough due to the low quality of included trials. Further large-sample and multi-center studies are needed.
Mesenchymal stem cells (MSC) are considered to have important value in the treatment of various diseases because of their low immunogenicity, transferability, and strong tissue repair capacity. Stromal cell derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) pathway plays an important role in migration of MSC. The induction of homing of MSC to retina by regulating SDF-1/CXCR4 may exert the curative effect on diabetic retinopathy to greatest exent.
Diabetic retinopathy (DR) is one of the microvascular complications of diabetes mellitus causing severe visual impairment, and it is the main cause of blindness in adults. Metabolic abnormalities play an important role in the occurrence and development of DR, including the abnormal levels of glucose metabolism, lipid metabolism, amino acid metabolism and purine metabolism, which indicate that there are disorders of phosphopentose pathway, arginine metabolism pathway, polyol pathway and ascorbic acid pathway in the progression of DR. Metabolomics has great advantages in exploring the pathogenesis and diagnosis of DR, helping to identify the characteristic metabolic changes of DR And discover potential biomarkers. However, the existing metabolomics studies on DR have some limitations, such as the potential biomarkers found in some studies are difficult to verify in other studies due to differences in race, age, gender and sample size. There are few studies on biomarkers at different stages of DR. Therefore, in the future, multi-center and large-scale clinical studies are needed to screen out biomarkers with practical clinical diagnostic value.
