title: Deleterious role of anti-high mobility group box 1 monoclonal antibody in retinal ischemia-reperfusion injury.
abstract: OBJECTIVE
  To investigate the effect of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) against ischemia-reperfusion injury in the rat retina.
  
  
  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.
authors: Department of Ophthalmology, Kagawa University, Japan.
authors: Hongwei
authors: H
authors: Yang
authors: Shenyang
authors: S
authors: Yang
authors: Kazuyuki
authors: K
authors: Hirooka
authors: Ye
authors: Y
authors: Liu
authors: Tomoyoshi
authors: T
authors: Fujita
authors: Kouki
authors: K
authors: Fukuda
authors: Takehiro
authors: T
authors: Nakamutra
authors: Toshifumi
authors: T
authors: Itano
authors: Jiyong
authors: J
authors: Zhang
authors: Masahiro
authors: M
authors: Nishibori
authors: Fumio
authors: F
authors: Shiraga
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D004596:Electroretinography; D005500:Follow-Up Studies; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012164:Retinal Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000911:Antibodies, Monoclonal; D024243:HMGB1 Protein; D017382:Reactive Oxygen Species