title: Suppression of retinal neovascularization by the iNOS inhibitor aminoguanidine in mice of oxygen-induced retinopathy.
abstract: BACKGROUND
  Retinal neovascularization (NV) is a major cause of blindness associated with ischemic retinal disorders. Our study was focused on evaluating the inhibitory effect of aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase (iNOS), on retinal NV in mice of oxygen-induced retinopathy (OIR).
  
  
  METHODS
  An OIR model was established with 7-day-old C57BL/6J mice. One day before and 1 and 3 days after being returned to the room air, the right eyes were injected intravitreally with bevacizumab, AG or bevacizumab+AG respectively. The left eyes were injected with normal saline (NS) as control. The mice were killed at postnatal day 17 (P17). The effects of AG or bevacizumab on iNOS or VEGF expressions were evaluated by RT-PCR and immunohistochemistry. Retinal NV was examined by fluorescein angiography, and was quantified histologically by CD34 immnunostaining at P17.
  
  
  RESULTS
  Compared with NS-treated eyes, retinal VEGF and iNOS mRNA expressions were significantly reduced in AG- and bevacizumab+AG-treated eyes; whereas in bevacizumab-treated eyes, retinal VEGF mRNA expression increased and iNOS mRNA expression remained unchanged. The above changes were confirmed by immunohistochemical study. The generalized decrease in both VEGF and iNOS distributions in mice retina treated with AG or bevacizumab+AG was demonstrated by immunohistochemistry. Retinal NV was significantly reduced in all three groups treated with bevacizumab, AG or bevacizumab+AG, when compared with NS-treated eyes.
  
  
  CONCLUSIONS
  iNOS activation plays a pathological role in retinal NV in a mouse model of ischemic retinopathy. Administration of AG significantly suppressed retinal NV. Therefore, AG appears to be a novel and effective therapeutic approach for retinal NV.
authors.affiliation: Department of Ophthalmology, Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jingfa
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guan
authors.forename: Shisheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhu
authors.forename: Guo-Tong
authors.initials: GT
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005451:Fluorescein Angiography; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007267:Injections; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010100:Oxygen; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014822:Vitreous Body
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen; C004479:pimagedine