O-linked N-acetylglucosamine (O-GlcNAc) glycosylation is an important form of post-translational protein modification, mainly intracellular. It is closely related to cellular signaling pathways, and is involved in signal transduction, gene transcription and other important biological processes. Studies have found that O-GlcNAc glycosylation is directly related with diabetic retinopathy (DR), further studies may help us to uncover the DR mechanism, and develop new strategies for the diagnosis and treatment of this disease.
Microvesicles (MVs) is small membrane vesicles released from different cell types under different conditions. Studies have shown that MVs may mediate vascular inflammation, angiogenesis, and other pathological processes. MVs may play an important role in the pathogenesis of diabetic retinopathy (DR) by mediating endothelial cell injury, thrombosis and neovascularization. The plasma MV level may be an effective parameter to monitor the development of DR. This article will summarize the research progress of the relationship between MVs and DR in recent years.
Diabetic retinopathy is a serious complication of diabetes and is the leading cause of blindness in people with diabetes. At present, there are many views on the pathogenesis of diabetic retinopathy, including the changes of retinal microenvironment caused by high glucose, the formation of advanced glycation end products, oxidative stress injury, inflammatory reaction and angiogenesis factor. These mechanisms produce a common pathway that leads to retinal degeneration and microvascular injury in the retina. In recent years, cell regeneration therapy plays an increasingly important role in the process of repairing diseases. Different types of stem cells have neurological and vascular protection for the retina, but the focus of the target is different. It has been reported that stem cells can regulate the retinal microenvironment and protect the retinal nerve cells by paracrine production, and can also reduce immune damage through potential immunoregulation, and can also differentiate into damaged cells by regenerative function. Combined with the above characteristics, stem cells show the potential for the repair of diabetic retinopathy, this stem cell-based regenerative therapy for clinical application provides a pre-based evident. However, in the process of stem cell transplantation, homogeneity of stem cells, cell delivery, effective homing and transplantation to damaged tissue is still a problem of cell therapy.
Objective To analyze the expression of apoptosis-related genes of retinal blood vessel in early diabetic rats by gene chip technology. Methods To make diabetic rat model by intraperitoneal injection of streptozotocin (STZ). On the 6th week after blood pressure increased, 10 rats were executed in Diabetic group and normal control group respectively. 20 retinal blood vessels were extracted and the RNA was isolated. The probe was made of alpha;-32 P-deoxyadenosine triphosphate (dATP)-labeled sample which hybridized 1176 nylon chips, and then analyzed by software. Three different expression genes were selected to verify by reverse transcription polymerase chain reaction (RT-PCR). Results On the 6th week, 136 （11.5％） genes were differentially expressed ［up-regulated genes were 90(7.6%), down-regulated genes were 46(3.9%)］in diabetic group. These genes involved into different groups according to their function. Especially in 72 apoptosis-related genes, 15 genes were differentially expressed. The up-regulated genes were some TNF receptor family members such as TNFRSF12, TRAIL, TNFRSF9, FADD；Bcl-2 family members such as bcl-w, bax, bak1 and AKT. The down-regulated genes were FAF1 which related to fas. Conclusions The expression of retinal vascular gene in early diabetic rats has been changed complicatedly. In particular, the multiple apoptosis-related genes have been changed in early diabetic, and most of them are at the upstream of apoptosis pathway. These findings indicate that the development of diabetic retinopathy is associated with multiple signaling pathways leading to apoptosis, while the alterations on the level of molecular biochemistry are still limited in apoptosis induction period. （Chin J Ocul Fundus Dis，2008，24：244-248）
Objective To observe the expression of N-cadherin in streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) ratsprime;retinae. Methods Celiac injection with 65 mg/kg STZ was performed on 20 rats to set up the diabetic model, and celiac injection with the same volume citrate buffer was performed on other 20 SD rats as the control. Vascular permeability was detected by Evans blue method. The expression of N-cadherin in both normal and STZ-induced diabetic ratsprime;retinae and trypsinase-digested retinal microvessels were detected by immunohistochemistry method and Western blotting analysis. Results Retinal vascular permeability increased 68%, 91% and 125% 4, 8, and 12 weeks, respectively, after diabetic models was induced (Plt;0.005). In the control group, the expression of N-cadherin was detected in the outer and inner plexiform layer, inner nuclear layer，ganglion cell layer,internal limiting membrane and between retinal endothelial cells and pericytes. However, the expression of N-cadherin significantly decreased in STZ-induced diabetic rats retinae at the 12th week. The results of Western blotting analysis showed that the expression of N-cadherin obviously decreased as the diabetic retinopathy developed. Conclusion The decrease of expression of Ncadherin in the retinae of STZ-induced diabetic rats suggests that N-cadherin may participate in the development of diabetic retinopathy at the early stage. (Chin J Ocul Fundus Dis,2007,23:269-272)
Dyslipidemia plays an important role in the pathogenesis of diabetic retinopathy (DR).Apreliminary study found that low-density lipoprotein cholesterol, apolipoprotein (Apo)Band ApoB/ Apo A1 ratio were positively correlated with DR, while high-density lipoprotein cholesterol, Apo A1 was negatively correlated with DR and proliferative DR. Reducing the blood fats to be helpful to DR control. However, the mechanism of hyperlipidemia in the pathogenesis of DR, the reason of dyslipidemia in diabetic patients and the interaction between hyperglycemia and hyperlipidemia in DR are not clear yet. Moreover, there is no predictive indicators related to blood lipid for DR. Understanding the relationship between dyslipidemia and DR can provide definite evidence for fat-reducing therapy for DR control.
Objective To determine the association of -429T/C and G1704T polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy (PDR). Methods Case-control study. From the Beijing Desheng Diabetic Eye Study cohort of 1467 patients with type 2 diabetes mellitus (T2DM),atotal of 97 patients with PDR and 105 diabetic patients without retinopathy (DWR, duration of diabetes 15 years) were included for this study. Questionnaires were collected and general ophthalmologic examinations were performed. Biochemical analysis was conducted. DNA was extracted from peripheral venous blood. The -429T/C and G1704T single nucleotide polymorphisms were detected by the means of PCR-restrication fragment length polymorphisms. Results The frequency distribution of -429T/C in DWR group was 81.0% in TT, 16.1% in TC, 2.9% in CC. The frequency distribution of -429T/C in PDR group was 77.3% in TT, 20.6% in TC, 2.1% in CC. There was no significant statistical difference between the two groups (χ2=0.40, P > 0.05). Frequency of the -429T/C minor alleleCin the DWR and PDR group were 11.0% and 12.4%, respectively, with no significant statistical difference between the two groups (χ2=0.20，P > 0.05). The frequency distribution of G1704T in DWR group was 66.7% in GG, 29.5% in GT, 3.8% in TT. The frequency distribution of G1704T in PDR group was 78.4% in GG, 21.6% in GT. There was no significant statistical difference between the two groups (χ2=3.44, P > 0.05). Frequency of the G1704T minor alleleTin the DWR and PDR group were 18.6% and 10.8%, respectively, in which significant difference was found within the two groups (χ2=4.79, OR=1.88，95%CI: 1.06 - 3.33, P > 0.05). Conclusions G1704T polymorphism is associated with PDR presence and 1704G allele may increase the risk of PDR.
Objective To investigate the relationship between subclinical hypothyroidism (SCH) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 792 patients of T2DM were enrolled in the study. There were 448 males and 344 females, with an average age of (54.13±13.06) years. The average duration of diabetes was (8.03±6.70) years. The patients were grouped according to the degree of DR and thyroid function. Among them, 483 patients (61.0%) were no DR, 240 patients (30.3%) were mild DR, 69 patients (8.7%) were severe DR. 725 patients (91.5%) were normal thyroid function, 67 patients (8.5%) were SCH. The prevalence of SCH among no DR group, mild DR group and severe DR group was compared. And the prevalence of DR between normal thyroid function group and SCH group was compared. Logistic regression analysis was used to estimate the association between SCH and DR. Results No significant differences among the three groups (no DR group, mild DR group, severe DR group) were found in the prevalence of SCH (χ2=1.823,P=0.402). There were no significant differences in the incidences of DR between normal thyroid function group and SCH group (χ2=1.618,P=0.239). Logistic regression analysis demonstrated that SCH was not significant associated with DR [mild DR: odds ratio (OR)=1.361, 95% confidence interval (CI)=0.773−2.399,P=0.286; severe DR:OR=1.326, 95%CI=0.520−3.384,P=0.555; DR:OR=1.353, 95%CI=0.798−2.294,P=0.261). Conclusion SCH is not significant associated with DR in patients with T2DM.