DIBI是一种聚合羟基吡啶酮铁螯合剂，可减轻局部和全身内毒素诱导的葡萄膜炎中的眼部炎症。

DIBI, a polymeric hydroxypyridinone iron chelator, reduces ocular inflammation in local and systemic endotoxin-induced uveitis.

作者信息

Arora N, Caldwell A, Wafa K, Szczesniak A, Caldwell M, Al-Banna N, Sharawy N, Islam S, Zhou J, Holbein B E, Kelly M E M, Lehmann Ch

机构信息

Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.

Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.

出版信息

Clin Hemorheol Microcirc. 2018;69(1-2):153-164. doi: 10.3233/CH-189109.

DOI:10.3233/CH-189109

PMID:29630535

Abstract

BACKGROUND/OBJECTIVE: Non-infectious uveitis is an inflammatory disease of the eye commonly treated by corticosteroids, though important side effects may result. A main mediator of inflammation are oxygen free radicals generated in iron-dependent pathways. As such, we investigated the efficacy of a novel iron chelator, DIBI, as an anti-inflammatory agent in local and systemic models of endotoxin induced uveitis (EIU).

METHODS

Firstly, the effects of DIBI in systemic EIU in Lewis rats were established. 2 hours post intravenous LPS or LPS/DIBI injections, leukocyte activation and functional capillary density (FCD) were examined using intravital microscopy (IVM) of the iridial microcirculation. Secondly, the toxicity of DIBI was evaluated in BALB/C mice for both acute and chronic dosages through gross ocular examination, intraocular pressure measurements and hematoxylin-eosin staining of ocular tissue. Lastly, three groups of BALB/C mice, control, LPS or DIBI + LPS, were studied to evaluate the effectiveness of DIBI in treating local EIU. Five hours post-local intravitreal (i.v) injection, leukocyte activation and capillary density were examined via IVM.

RESULTS

Treatment of systemic EIU with DIBI resulted in a reduction of leukocyte activation and FCD improvement within the iridial microcirculation. Toxicity studies suggested that acute and chronic DIBI administration had no adverse effects in the eye. In the local EIU model, DIBI was shown to reduce leukocyte activation and restored the FCD/DCD ratio, providing evidence for its anti-inflammatory properties.

CONCLUSIONS

Our study has provided evidence that DIBI has anti-inflammatory effects in experimental uveitis. Additionally, no local ocular toxicity was observed.

摘要

背景/目的：非感染性葡萄膜炎是一种眼部炎症性疾病，通常用皮质类固醇治疗，但可能会产生重要的副作用。炎症的主要介质是铁依赖性途径中产生的氧自由基。因此，我们研究了一种新型铁螯合剂DIBI作为内毒素诱导性葡萄膜炎（EIU）局部和全身模型中的抗炎剂的疗效。

方法

首先，确定DIBI在Lewis大鼠全身EIU中的作用。静脉注射LPS或LPS/DIBI后2小时，使用虹膜微循环的活体显微镜检查（IVM）检查白细胞活化和功能性毛细血管密度（FCD）。其次，通过大体眼部检查、眼压测量和眼部组织苏木精-伊红染色，评估DIBI在BALB/C小鼠中的急性和慢性剂量毒性。最后，研究三组BALB/C小鼠，即对照组、LPS组或DIBI + LPS组，以评估DIBI治疗局部EIU的有效性。局部玻璃体内（i.v.）注射后5小时，通过IVM检查白细胞活化和毛细血管密度。