The role of leukocyte in the pathogeuesis of diabctic retiuoparthy

最近，白细胞被认为在炎症条件下发挥中心作用，如缺血再灌注损伤和内毒素诱导的葡萄膜炎。在炎症部位，循环中的白细胞被认为是通过白细胞-内皮细胞相互作用的多步骤级联作用而发生的，包括顺序滚动、牢固的粘连和向炎症组织的迁移。在这种多步骤的白细胞渗透过程中，每个过程都由不同的黏附分子介导，并受到严格的调控。糖尿病与短暂性脑缺血后更大的神经损伤有关。采用链脲佐菌素诱导的糖尿病大鼠4周模型，研究缺血再灌注损伤后白细胞与内皮细胞的相互作用。与非糖尿病大鼠相比，糖尿病大鼠在整个再灌注期内的白细胞滚动和聚集明显受到抑制。此外，无论是缺血前胰岛素治疗还是d…更多的糖尿病大鼠和非糖尿病大鼠的缺血前葡萄糖输注对再灌流期间白细胞与内皮细胞的相互作用有显著影响。诱导缺血前的高血糖浓度并不会加剧白细胞对缺血后视网膜损伤的影响。综上所述，糖尿病视网膜在短暂性缺血后表现出白细胞-内皮细胞相互作用的抑制，这可能是由于在诱导糖尿病期间发展的一种适应性机制。在ATIII的治疗中，白细胞沿视网膜静脉滚动基本上被抑制，抑制了随后的白细胞向玻璃体腔的渗透。同样，AT11治疗可显著减少白细胞渗入和蛋白渗入房水。在注射内毒素后，大鼠虹膜睫状体和视网膜中P-选择素mRNA的表达水平均显著降低。ATIII治疗可显著抑制LPS诱导的炎症反应，其对P-选择素表达的抑制作用可能通过抑制白细胞滚动而减轻白细胞的浸润。目前的研究结果表明，ATIII对治疗顽固性葡萄膜炎具有治疗效力。较少

Recently, leukocytes are thought to play a central role in inflammatory conditions such as ischemia-reperfusion injury and endotoxin-induced uveitis. At inflammatory sites, the recruitment of circulating leukocytes out of the vessels is thought to occur through a multistep cascade of leukocyte-endothelial interactions, involving sequential rolling, firm adhesion, and transmigration into inflamed tissues. During this multistep cascade of leukocyte infiltration, each process is mediated with distinct adhesion molecules and regulated elaborately.Diabetes is associated with greater neural damage after transient cerebral ischemia. Using rats with streptozotocin-induced diabetes of 4 weeks duration, we investigated leukocyte-endothelial cell interactions after ischemia-reperfusion injury. Leukocyte rolling and accumulation throughout the period of reperfusion was significantly suppressed in diabetic rats compared with non-diabetic rats. In addition, neither preischemic insulin treatment to d … More iabetic rats nor preischemic glucose infusion to non-diabetic rats had a significant influence on leukocyte-endothelial cells interactions during reperfusion. High blood glucose concentration before induction of ischemia did not exacerbate leukocyte involvement in the postischemic retinal injury. In conclusion, diabetic retina showed suppressed leukocyte-endothelial cells interactions after transient ischemia, perhaps due to an adaptive mechanism that developed during the period of induced diabetes.EIU is characterized by blood ocular barrier disruption and leukocyte infiltration. The treatment with ATIII, leukocyte rolling was substantially inhibited along the retinal veins, suppressing subsequent leukocyte infiltration into the vitreous cavity. Similarly, leukocyte infiltration and protein leakage into the aqueous humor were significantly reduced with ATlll treatment. The levels of P-selectin mRNA expression in both iris-ciliary body and retina, which were upregulated after LPS injection, were substantially lower in the ATIII-treated rats. ATIII treatment significantly inhibited inflammatory reactions induced with LPS.Its suppressive effects on P-selectin expression could contribute to the attenuation of leukocyte infiltration, possibly by inhibiting leukocyte rolling. The current findings suggest the therapeutic potency of ATIII for the treatment of inveterate veitis. Less