Iontophoresis of dexamethasone in the treatment of endotoxin-induced-uveitis in rats
Iontophoresis of dexamethasone in the treatment of endotoxin-induced-uveitis in rats
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DOI：
10.1006/exer.1997.0364
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发表时间：
1997-10-01
影响因子：
3.4
通讯作者：
DeKozak, Y
中科院分区：
文献类型：
--
作者：
BeharCohen, FF;Parel, JM;DeKozak, Y
本研究的目的是评估库仑控制离子透入系统（CCI）局部递送皮质类固醇治疗葡萄膜炎的疗效。将CCI给药地塞米松（Dex）的治疗效果与全身注射和在没有电流的情况下用离子透入仪局部应用进行比较。评估是在内毒素诱导的葡萄膜炎（EIU）模型的治疗中进行的，以及对虹膜/睫状体和视网膜中TNF基因表达的影响以及对房水和玻璃体中TNF水平的影响。在LPS注射时或5小时后给药。对于离子导入，我们使用1ml储层电极覆盖角膜、角膜缘和巩膜的第一毫米。在4分钟内，施加的电流为400 μ A，总表面电荷为0.4 C cm（-2）。通过临床检查、眼内炎症细胞的组织学切片计数以及测量房水和玻璃体中的蛋白质水平来评估EIU。RT-PCR检测虹膜、睫状体和视网膜中tnf - α基因的表达。CCI给药Dex对EIU患者血清tnf - α水平的影响。我们的研究结果表明，CCI局部给药Dex与全身给药一样有效地抑制眼内炎症的前后征象，而对全身TNF水平没有影响。眼前、眼后段蛋白渗出、TNF水平及细胞浸润均受到抑制。tnf - α基因的表达在眼前段和眼后段均受到抑制。CCI仪器未造成临床和组织学损害。综上所述，在CCI中给药右美托咪唑对眼后段和眼前段都有治疗效果，并且可能是严重眼部炎症中全身给药糖皮质激素的可行替代方案。(C) 1997学术出版社有限公司
The purpose of this study was to evaluate the efficacy of a Coulomb Controlled Iontophoresis system (CCI) in the local delivery of corticosteroids for the treatment of uveitis.The therapeutic efficacy of Dexamethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the absence of electrical current. The evaluation was done in the treatment of the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered either at the time of LPS injection or 5 hours later. For iontophoresis, we used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current was of 400 mu A during four minutes with a total surface charge of 0.4 C cm(-2). EIU was evaluated by clinical examination, by counts of intraocular inflammatory cells on histological sections, and by measuring the protein levels in the aqueous humor and in the vitreous. The TNF-alpha gene expression in the iris and ciliary body, and in the retina was evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-alpha in EIU. Our results demonstrated that local administration of Dex by CCI inhibited anterior and posterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anterior and posterior segments of the eye, the protein exudation, TNF levels and the cellular infiltration were inhibited. The TNF-alpha gene expression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CCI apparatus.In conclusion, CCI administration of Dex allows for a therapeutic effect on the posterior as well as the anterior segment of the eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations. (C) 1997 Academic Press Limited.