Diabetic retinopathy (DR) isacommon cause of blindness, its occurrence and development are the synergic results of multiple factors. Current studies suggest that inflammation and inflammatory factor has an important role in the pathogenesis of DR. The occurrence and development of DR are closely related with interleukins, intercellular adhesion molecules, hasten factors, tumor necrosis factor, C-reactive protein etc. Mesenchymal stem cells (MSCs) are pluripotent cells derived from the mesoderm and have multiple differentiation potentials, and anti-inflammatory and immunosuppressive function. Recent studies shown that MSCs transplantation can protect damaged retina by inflammatory regulation, which becomeanew research direction for DR treatment.
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.
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
Objective To observe the effects of simvastatin on endothelial progenitor cells (EPCs) from peripheral blood and retinopathy in rats with diabetic retinopathy (DR). Methods Eighty male Wistar rats were divided into normal control group (group A), DR model group (group B), DR with placebo group (group C), DR with simvastatin group (group D), with twenty rats in each group. The rats in group C and D received streptozotocin (STZ) injection to induce diabetic retinopathy. The rats in the group A and B were not intervened. The rats were gavaged with 20 mg/kg simvastatin (group D) or same volume of distilled water (group C) once a day. Flow cytometry was used to identify and count the number of EPCs from peripheral blood at the 1st，4th and 12th week after injection. Evans blue perfusion was used to detect the bloodretinal barrier (BRB) permeability. Immunohistochemical staining was used to observe the expression of CD31 in the retina. Real-time reverse transcriptionpolymerase chain reaction (RT-PCR) was used to measure the mRNA expression of eNOS, iNOS and Ang-1. The correlation between changes of EPCs and DR morphological changes was analyzed. Results At the 1st，4th and 12th week after injection, compared with the group A, the number of EPCs was decreased in group C; Compared with the group B and C, the number of EPCs was increased in group D (t=4.967, 5.648, 6.688, 6.042, 7.392, 7.454;P＜0.05); there was no statistical difference of EPCs number between group B and C (t=0.525, -0.249, -0.619; P＞0.05), group A and D (t=6.733, 2.794, -5.535; P＜0.05) respectively. The structure of retina was continuous and its capillary structure was normal in control group. The retinal layers were edema and the retina developed telangiectatic vessels and many ganglion cells developed vacuolar degeneration in group B and C. The layers tissue of retina was less edema and gradually arranged in group D. The BRB permeability was significantly increased in group B and D compared with group A. The BRB permeability was significantly decreased in group D compared with group B (F=65.808，P＜0.05). The CD31 expression in group D was obviously higher than that in group A, B and C (F=24.799，P＜0.05). The eNOS expression in group B was obviously lower than that in group A, while in group D was obviously higher than that in group B (t=-2.750，2.230；P＜0.05). The iNOS and Ang-1 expression in group B were obviously higher than those in group A, while in group D was obviously lower than that in group B (t=3.881，-1.144，4.244，-1.458；P＜0.05). There was no difference in BRB permeability, eNOS, iNOS and Ang-1 expression between group B and C (t=0.480,-0.877, 0.062, 0.220; P＞0.05). Conclusions Simvastatin could mobilize DR rats peripheral blood EPCs, induce migration and differentiation of retinal endothelial cell, slow down the DR progress by regulating the expression of endothelium factors such as eNOS and iNOS.
Objective To investigate the amounts of endothelial progenitor cells (EPCs) in peripheral blood of patients with proliferative diabetic retinopathy (PDR). Methods Forty patients with PDR (PDR group), thirty patients with type 2 diabetes mellitus (DM) without DR (DM group), and twenty age-matched normal subjects (control group) were enrolled in this study. Blood samples were treated by repeated centrifugation and stained with monoclonal antibodies. At least 2times;105 cells were analyzed by flow cytometry. EPCs were identified by CD34 and CD133 antibody. The correlation between EPCs numbers and DR duration, glycosylated hemoglobin, serum lipids was analyzed. Results The number of EPCs in PDR, DM and control group were (49plusmn;12)、(35plusmn;11)、(90plusmn;25) cells/ml respectively, the difference was statistically significant (F=56.260, P=0.000). There was a positive correlation between EPCs numbers and DR duration (r=0.564, P＜0.05). However there was no correlation between EPCs numbers and glycosylated hemoglobin (r=-0.170, P＞0.05) or triglyceride levels (r=0.261, Pgt;0.05). Conclusions The number of EPCs in peripheral blood of PDR patients was decreased. EPCs might play an important role in the pathogenesis of PDR.
Objective To evaluate the efficacy of perioperative management for vitrectomy of patients with severe systemic disease. Methods The clinical data of 21 patients (22 eyes) with severe systemic disease who underwent vitrectomy were retrospectively analyzed. There were 11 patients (12 eyes) with proliferative diabetic retinopathy, 9 patients (9 eyes) with rhegmatogenous retinal detachment, and 1 patient (1 eye) with intraocular lens dislocation. The preoperative visual acuity ranged from hand movement to 0.6. There were 4 patients (5 eyes) with renal insufficiency undergoing renal dialysis, 7 patients (7 eyes) with myocardial infarction or coronary artery stenosis received cardiac bypass surgery or coronary stent implantation, 2 patients (2 eyes) with severe arrhythmia received cardiac pacemaker implantation or radiofrequency catheter ablation, 5 patients (5 eyes) with cerebral infarction, 2 patients (2 eyes) with hemophilia, and 1 patient (1 eye) with aplastic anemia. For patients with cardiac bypass surgery or coronary stent implantation, anticoagulants were switch to low molecular heparin at 7 days before vitrectomy. For patients undergoing renal dialysis, 0.4 ml low molecular heparin was used during renal dialysis at one day before vitrectomy, protamine and heparin were administered after vitrectomy. Prothrombin complex was infused from 1 day before surgery to 5 days after surgery for Hemophilia B patients.6 patients (6 eyes) underwent phacoemulsification, and 1 patient (1 eye) underwent ciliary sulcus fixed intraocular lens implantation. 14 patients (14 eyes) underwent silicone oil tamponade,5 patients (6 eyes) underwent C3F8 tamponade.Results The postoperative visual acuity ranged from light perception to 1.0. The vision increased in 18 patients (19 eyes), unchanged in 2 patients (2 eyes), and decreased in 1 patient (1 eye). The retina attached in all eyes postoperatively. The postoperative complications mainly included mild anterior chamber bleeding in 4 patients (4 eyes), severe anterior chamber bleeding in 1 patient (1 eye), mild retinal hemorrhage in 2 patients (2 eyes), optic disc bleeding in 2 patients (3 eyes), temporary elevation of intraocular pressure in 1 patient (1 eye), and neovascular glaucoma in 1 patient (1 eye). Serum creatinine increased in 1 patient and hypertension in 1 patient within 1 week postoperatively. Conclusions Severe systemic disease is not an absolute contraindication for vitrectomy. Vitrectomy can be successfully performed with better outcomes under the proper perioperative management of systemic disease.
ObjectiveTo investigate the effects of migration and expression from chemokine receptor 4 (chemokine receptor-4, CXCR4) of rat bone marrow mesenchymal stem cells (BMSCs) which were pretreated by atorvastatin (ATV) in vitro.MethodsIsolated, cultivated, identified the BMSCs, pretreated P4-P6 of BMSCs with different concentrations of ATV for 12 hours. The experimental group was divided into control group, 0.1 nM/L (group 0.1 nM), 1 nM/L (1 nM group), 10 nM/L (10 nM group), 100 nM/L (100 nM group), 1 000 nM/L (1 000 nM group). The mRNA and protein of CXCR4 were determined by real time-polymerase chain reaction and Western blot. Immunofluoreseence assay were used to detect the expression levels of CXCR4. The migration ability of BMSCs were measured by transwell chamber.ResultsImmunofluoreseence assay showed the protein level of CXCR4 of group 1 nM and 10 nM were significantly higher than the other group. RT-PCR and Western blot showed the protein and mRNA level of CXCR4 in 10 nM was higher than that in group 1 nM. The migration ability of group 10 nM was higher than 1 nM and control group.ConclusionsATV can be dose-dependent promote expression levels of CXCR4 of BMSCs cultivated in vitro.
Objective To observe the changes in the number and activity of endothelial progenitor cell (EPC) from peripheral blood in patients with diabetic retinopathy (DR). Methods Twelve patients with DR (DR group), 18 patients with diabetic mellitus (DM) without DR (DM group), and 15 patients with age-related cataract without DM (control group) were enrolled in this study. Peripheral blood mononuclear cells were isolated by density gradient centrifugation. After 10 days culture, positive rate of EPC was counted by flow cytometry, proliferation, adhesion and migration activities were assayed by MTT chromatometry, adhesion activity assay essay and Transwell assay. Results Flow cytometric test showed that positive rate of EPC in patients of DR group, DM group and control group was (37.370plusmn;2.501)%, (30.130plusmn;3.245)% and (45.190plusmn;1.287)%. There was a significant difference between these three groups (F=27.690, P=0.001). MTT chromatometry showed that A-values of DR group, DM group and control group were 0.330plusmn;0.047, 0.225plusmn;0.042 and 0.120plusmn;0.029. There was a significant difference between these three groups(F=29.327，P=0.000). Adhesion activity assay essay showed that EPC numbers in DR group, DM group and control group were 76.400plusmn;7.503, 51.167plusmn;6.646 and 26.500plusmn;7.853. There was a significant difference between these three groups (F=56.612, P=0.000). Transwell assay showed that EPC numbers in DR group, DM group and control group were 23.600plusmn;6.504, 20.833plusmn;4.491 and 12.000plusmn;2.944. There was a significant difference between these three groups (F=6.477, P=0.012). Conclusion EPC from peripheral blood in patients with DR exhibit reduced numbers and impaired proliferation, adhesion and migration activity.