Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina
Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina
复制标题
DOI：
10.1167/iovs.04-0905
复制
发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Yoshimura, N
中科院分区：
文献类型：
--
作者：
Tamura, H;Miyamoto, K;Yoshimura, N
目的.最近，玻璃体内注射皮质类固醇已被广泛用于治疗糖尿病性黄斑水肿，其结果是有利的。然而，确切的机制仍不清楚。目前研究的假设是玻璃体内注射皮质类固醇可以通过改善血视网膜屏障（BRB）的破坏，抑制白细胞停滞（leukostasis）来改善糖尿病视网膜水肿。通过腹腔注射链脲佐菌素（75 mg/kg）在6周龄雄性Long-Evans大鼠中诱导糖尿病。诱导糖尿病后3周，玻璃体内注射地塞米松（40 μ g/10 μ L）。在玻璃体内注射后2天，通过吖啶橙子白细胞荧光照相术在体内计数累积的白细胞，并通过测量视网膜血管通透性来评估BRB的分解。同时检测视网膜细胞间粘附分子（ICAM）-1的mRNA表达和蛋白水平。糖尿病组视网膜白细胞数一度升高，注射地塞米松后下降31.6%（P = 0.0001）。糖尿病组的BRB分解水平也升高，地塞米松注射后抑制了61.1%（P = 0.0046）。糖尿病组ICAM-1 mRNA表达及蛋白表达水平均明显上调，地塞米松治疗组分别下调70.0%（P < 0.0001）和56.4%（P = 0.0003）。玻璃体内注射皮质类固醇通过抑制白细胞在糖尿病视网膜中的募集来改善糖尿病视网膜水肿。
PURPOSE. Recently, intravitreal injection of corticosteroids has been in wide use as a treatment for diabetic macular edema, and the outcomes have been favorable. However, the exact mechanism remains unclear. The hypothesis for the current study was that intravitreal corticosteroids may improve diabetic retinal edema by amelioration of blood-retinal barrier (BRB) breakdown, by inhibiting leukocyte stasis (leukostasis).METHODS. Diabetes was induced in 6-week-old male Long-Evans rats by intraperitoneal injection of streptozotocin (75 mg/kg). Three weeks after induction of diabetes, intravitreal injection of dexamethasone (40 mu g/10 mu L) was performed. At 2 days after intravitreal injection, accumulated leukocytes were counted in vivo by acridine orange leukocyte fluorography, and BRB breakdown was evaluated by measurement of retinal vascular permeability. The mRNA expression and protein levels of intercellular adhesion molecule (ICAM)-1 in the retina were also studied.RESULTS. The number of leukocytes accumulated in the retina, once increased in the diabetic group, was decreased by 31.6% (P = 0.0001) after dexamethasone injection. The level of BRB breakdown, also elevated in the diabetic group, was suppressed by 61.1% (P = 0.0046) after dexamethasone injection. The level of ICAM-1 mRNA expression and its protein, upregulated in the diabetic group, were downregulated by dexamethasone treatment by 70.0% (P < 0.0001) and 56.4% (P = 0.0003).CONCLUSIONS. Intravitreal injection of corticosteroids improves diabetic retinal edema through inhibiting leukocyte recruitment in the diabetic retina.