The role of leukocyte in the pathogeuesis of diabctic retiuoparthy

白细胞在糖尿病视网膜病变发病机制中的作用

• 批准号: 11671733
• 负责人: KIRYU Junichi
• 金额: $ 2.24万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671733/
• 关键词: leukocyte; retina; diabetes

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

最近，白细胞被认为在炎症状态如缺血-再灌注损伤和内毒素诱导的葡萄膜炎中起核心作用。在炎症部位，循环白细胞从血管中募集被认为是通过白细胞-内皮相互作用的多步级联发生的，包括连续滚动、牢固粘附和迁移到炎症组织中。在白细胞浸润的多步骤级联过程中，每个过程都由不同的粘附分子介导，并受到精心调控。使用链脲佐菌素诱导的糖尿病大鼠4周的持续时间，我们研究缺血再灌注损伤后白细胞-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间的白细胞滚动和积聚被显著抑制。此外，缺血前胰岛素治疗对缺血性心脏病的发生无明显影响。 ...更多信息 糖尿病大鼠和非糖尿病大鼠缺血前葡萄糖输注对再灌注期间白细胞-内皮细胞相互作用均具有显著影响。诱导缺血前的高血糖浓度不会加重缺血后视网膜损伤中的白细胞参与。总之，糖尿病视网膜短暂缺血后白细胞-内皮细胞相互作用受到抑制，这可能是由于在诱导糖尿病期间形成的适应性机制。EIU的特征是血眼屏障破坏和白细胞浸润。用ATIII处理，白细胞滚动基本上被沿着视网膜静脉抑制，抑制了随后白细胞浸润到玻璃体腔中。类似地，ATIII治疗显著减少白细胞浸润和蛋白质渗漏到房水中。在ATIII处理的大鼠中，虹膜睫状体和视网膜中的P-选择素mRNA表达水平在LPS注射后上调，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浸润。目前的研究结果表明ATIII治疗顽固性脉络膜炎的治疗效力。少

项目成果

N.Hiroshiba: "Radiation-induced leukocyte entrapment in the rat retinal microcirculation."Invest Ophthalmol Vis Sci. 40(6). 1217-1222 (1999)

N.Hiroshiba：“辐射诱导的白细胞滞留在大鼠视网膜微循环中。”Invest Ophasemol Vis Sci。

Miyamoto-K, Ogura Y.: "Pathogenetic potential of leukocytes in diabetic retinopathy."Seminars in Ophthalmol.. 14. 233-239 (1999)

Miyamoto-K、Ogura Y.：“白细胞在糖尿病视网膜病变中的致病潜力。”眼科研讨会 14. 233-239 (1999)

A.Tsujikawa: "In vivo evaluation of platelet-endothelial interactions in retinal microcirculation of rats."Invest Ophthalmol Vis Sci. 40(12). 2918-2924 (1999)

A.Tsujikawa：“大鼠视网膜微循环中血小板-内皮相互作用的体内评估。”Invest Ophamol Vis Sci。

A.Tsujikawa: "Leukocyte-endothelial cell interactions in diabetic retina after transient retinal ischemia."Am J Physiol Regulatory Integrative Corp Physiol. 279(3). 980-989 (2000)

A.Tsujikawa：“短暂性视网膜缺血后糖尿病视网膜中白细胞与内皮细胞的相互作用。”Am J Physiol Regulatory Integrative Corp Physiol。

A.Tsujikawa: "In vivo evaluation of platelet-endothelial interactions in retinal microcirculation of rats"Invest Ophthalmol Vis Sci. 40(12). 2918-2924 (1999)

A.Tsujikawa：“大鼠视网膜微循环中血小板-内皮相互作用的体内评估”Invest Ophamol Vis Sci。