Deleterious Role of Anti-high Mobility Group Box 1 Monoclonal Antibody in Retinal Ischemia-reperfusion Injury

作者：Yang Shenyang; Hirooka Kazuyuki^*; Liu Ye; Fujita Tomoyoshi; Fukuda Kouki; Nakamutra Takehiro; Itano Toshifumi; Zhang Jiyong; Nishibori Masahiro; Shiraga Fumio

来源：Current Eye Research, 2011, 36(11): 1037-1046.

DOI：10.3109/02713683.2011.594201

• Anti-HMGB1 mAb
• Retinal ischemia
• Reactive oxygen species
• Electroretinogram
• Retinal thickness

Purpose: To investigate the effect of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) against ischemia-reperfusion injury in the rat retina.
Materials and Methods: Retinal ischemia was induced by increasing and then maintaining intraocular pressure at 130 mmHg for 45 min. An intraperitoneal injection of anti-HMGB1 mAb was administered 30 min before ischemia. Retinal damage was evaluated at 7 days after the ischemia. Immunohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of anti-HMGB1 mAb. Dark-adapted full-field electroretinography (ERG) was also performed.
Results: Pretreatment with anti-HMGB1 mAb significantly enhanced the ischemic injury of the retina. HMGB1 expression increased at 6-12 h after ischemia in the retina. After the ischemia, production of ROS was detected in retinal cells. However, pretreatment with anti-HMGB1 mAb increased the production of ROS. On the seventh postoperative day, the amplitudes of both the ERG a- and b-waves were significantly higher in the vehicle group than in the groups pretreated with anti-HMGB1 mAb.
Conclusions: The current in vivo model of retinal injury demonstrated that anti-HMGB1 mAb plays a large deleterious role in ischemia-reperfusion injury. In order to develop neuroprotective therapeutic strategies for acute retinal ischemic disorders, further studies on anti-HMGB1 mAb function are needed.

• 出版日期2011-11
• 单位中国医科大学