| BACKGROUNDRrecent years, the prevalence of diabetes are increasing, the Diabetes Atlas data show that the number of patients with diabetes in China from2010’s43.15million, rising to98.4million in2013, ranking first in the world. Especially in Beijing, Shanghai and other developed regions including the Pearl River Delta, DM prevalence rate are close to the level of developed countries in Europe and America. DM and its associated complications of treatment and care will inevitably result in a heavy economic and social burden. Diabetic retinopathy, one of the most common microvascular complications of diabetes, is a reflection of diabetes metabolic disorders, endocrine and blood system damage in the retina. Globally, diabetic retinopathy is one of the world within the scope of labor population leading cause blindness in young adults, it is one of the reasons for elderly patients with blind eyes, has become a serious global problem.For China, it has been reported the DR prevalence rate ranges from16%to43.1%.In addition, the World Health Organization data show that the incidence of DR is increasing every year worldwide, and therefore, DR has become an urgent task for the Prevention of Blindness.The pathogenesis of diabetic retinopathy is a research hot spot and focus in recent years,and at the same time. The etiology of the complex brought difficulties to the prevention and treatment.DR is based on the incidence of long-term, chronic hyperglycemia, long-term high blood sugar which can damage the environment retinal vascular endothelium, causing a series of retinopathy, such as microaneurysms, hard exudates, cotton wool spots, neovascularization, retinal detachment or vitreous proliferation. However, DR specific complex pathogenesis is not clear. Generally agreed that the incidence of DR at home and abroad for a variety of cellular and molecular mechanisms of participation result. Currently, DR pathogenesis is mainly composed of the following hypothesis:biochemical part of the biological mechanisms, an immune mechanism of inflammation, oxidative stress theory, gene polymorphism and neural degenerative changes. Several mechanisms including mutual, reciprocal causation together constitute the complex pathogenesis system. In addition, studies have shown that, in the microenvironment of diabetes, the structure and function of a variety of cells in the retina exception occurs, including disorders of retinal vascular endothelial cells, ganglion cell apoptosis metabolism Muller abnormal cells, and pigment epithelial cells were varying degrees of damage. People gradually realized DR process is also a chronic inflammatory process, along with the activation and expression of inflammatory cytokines many anomalies. The latest international tends to as ’diabetic retinopathy’ which shows inflammatory injury, a series of processes including oxidative stress, apoptosis and cell proliferation, is the key to the development of diabetic retinopathy.In recent years, the relationship between DR and oxidative stress are more and more concerned about. Oxidative stress is the intra-cellular oxidation and antioxidant defense system imbalance, leading to increased production of reactive oxygen species and nitric oxide, thereby causing damage to abnormal metabolism of tissue cytokine activation and apoptosis, which play a key role in diabetic microvascular and macrovascular complications. Numerous studies indicate that in the early stage of diabetic retinopathy, ROS and nitric oxide product increase. Oxidative stress, especially disorders of retinal endothelial cell function and death plays an important roleon the development of DR.Heme oxygenase-1belongs to the heat shock protein family member, which is a rate-limiting enzyme heme metabolic processes, may play a role in the induction generated by the product. HO-1catalytic generation of free heme iron, carbon monoxide and biliverdin biliverdin and biliverdin reductase in effect, quickly converted into bilirubin. HO-1can be induced in many cases generated:oxidative stress such as ultraviolet radiation, and repair of ischemic metal, and a variety of cytokines can induce nitric oxide and so onPrevious studies have demonstrated that in vitro cell culture and animal models, HO-1in RPE cells, endothelial cells, photoreceptor cells, ganglion cells, Muller cells were expressed at increased its expression under stress. Studies have found that hemoglobin can effectively induce the expression of HO-1in diabetic rat retina’s, Muller cells may main responder cells to HO-1in the retina.Conventional wisdom holds that,HO-1has antioxidant, anti-inflammatory and anti-apoptotic cell protection. Oxidative stress can be induced HO-1generated at the fastest speed. The bilirubin is considered to be an effective scavenger of oxygen free radicals, oxidative stress response, has a protective effect on the cells. Free iron is believed to have a role in cell damage, but free iron can be combined into ferritin in vivo, ferritin involved in iron metabolism antioxidant effect.In recent years, however, it was found that, in additionto the protective effect in cells, but also HO-1has an important role in promoting the formation of new blood vessels. Vascular endothelial growth factor(VEGF), stromal cell-derived factor-1, etc. can induce the expression of HO-1to regulate neovascularization. And in the other hand, few years ago, VEGF inhibitors become the new anti-angiogenesis targeted therapies. It is mainly through the inhibition of angiogenesis antagonism, reducing vascular permeability, regulation of blood-retinal barrier permeability, so as to achieve the promotion of the retina absorb exudates.Ranibizumab(Lucentis) is a second generation recombinant humanized murine monoclonal anti-VEGF antibody fragment, the molecular weight is small, can better penetrate the retina, the vitreous bioavailability up to50%to60%, which is the only FDA-approved anti-VEGF drugs for the treatment of eye disease, and its overall effectiveness, safety, and after intravitreal injection of administration in the treatment of AMD has been demonstrated in numerous studies, all of which the human VEGF-A isoforms are specificity and affinity, the main mechanism of binding VEGF, vascular leakage and prevents the formation of new blood vesselsResearchers showed4-30days before Pars plana vitrectomy operation(PPV) receiving Lucentis treatment is easier for removing the membrane, while reducing occurrence of intraoperative bleeding and iatrogenic retinal breaks, but also significantly shortening the operation time. Therefore, we also collected the vitreous humor for patients with PDR after injection the Lucentis, for detecting the expression of HO-1.Another study found that the presence of abnormal expression of HO-1in the retinal cells and diabetic animal models cultured in high glucose. But HO-1expression in patients DR is unclear. In order to investigate the role of HO-1in the pathogenesis of DR, we observed HO1-expression in type2diabetic patients peripheral blood mononuclear cells, serum and vitreous humor of the liquid. In order to elucidate the pathogenesis of DR, seeking new therapeutic targets provide a theoretical basis and experimental basis.METHOD 1. All of the durations of the diabetes courses are greater than6months. Eighteen patients with non-diabetic retinopathy (DM-NDR), forty six patients with DR (DR group) and20healthy controls (control group) were included in this study. There were24patients with non-proliferative diabetic retinopathy (NPDR) and22patients with proliferative diabetic retinopathy (PDR). Peripheral Blood samples were obtained from all recruitments. HO-1mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). At the same time,We collected a total of34serum cases of diabetic patients,10patients withODM-NDR,10patients with NPDR,14patients with PDR and13healthy controls (control group) were included in this study.The expression levels of HO-1were analyzed by enzyme-linked immunosorbent assay (ELISA).2. We also chosethe vitreous humor from49patients who need PPV surgery.20patients with PDR,14patientswith proliferative vitreoretinopathy(PVR),9patients with idiopathic macular hole,6patients with PDR after Lucentis injection were included in this study.ELISA was used to analysis the HO-1expression.3. The correlation between theexpression of HO-1and some physical parameters was also analyzed.RESULTSl.The results of qRT-PCR showed that expressions of HO-1mRNA were significantly different among DR group, DM-NDR group and control group. The expression of HO-1mRNA in PDR group was significantly lower than those in the NPDR group. Compared with NPDR group, the expression of HO-1mRNA was significantly lower in PDR group.2.ELISA results found, HO-1expression in vitreous humor were significantly higher in PDRgroup compared with the idiopathic macular hole group.3.HO-1expression in DR patients with abnormal peripheral blood and vitreous humor, suggesting that HO-1may be involved in the development of diabetic retinopathy.4. There was a correlation between expression of HO-1mRNA and the systolic pressure,as well as the clucosylated hemoglobin.While in serum,there was a correlation between expression of HO-1and clucosylated hemoglobin,as well as the Creatinine.at last, there was a correlation between expression of HO-1and clucosylated hemoglobin,as well as the Creatinine.Metioned to the HO-1in vitreous humor,there was a there was no correlation between it and any physical parameters. |
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