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

• Published in: Current eye research 2011-11, Vol.36 (11), p.1037-1046
• Main Authors: Yang, Shenyang, Hirooka, Kazuyuki, Liu, Ye, Fujita, Tomoyoshi, Fukuda, Kouki, Nakamutra, Takehiro, Itano, Toshifumi, Zhang, Jiyong, Nishibori, Masahiro, Shiraga, Fumio
• Format: Article
• Language: English
• Subjects: Animals; Anti-HMGB1 mAb; Antibodies, Monoclonal - pharmacology; Disease Models, Animal; Electroretinogram; Electroretinography; Follow-Up Studies; HMGB1 Protein - biosynthesis; HMGB1 Protein - immunology; Immunohistochemistry; Male; Oxidative Stress - immunology; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reperfusion Injury - immunology; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Retina - metabolism; Retina - pathology; Retina - physiopathology; Retinal Diseases - immunology; Retinal Diseases - metabolism; Retinal Diseases - physiopathology; Retinal ischemia; Retinal thickness
• ISSN: 0271-3683; 1460-2202
• DOI: 10.3109/02713683.2011.594201

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.