title: Relative contribution of VEGF and TNF-alpha in the cynomolgus laser-induced CNV model: comparing the efficacy of bevacizumab, adalimumab, and ESBA105.
abstract: OBJECTIVE
  To compare the relative contribution of VEGF and TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in monkeys and to exploit the feasibility of topical use of suitable antibody fragments for the prevention of experimental CNV.
  
  
  METHODS
  To induce experimental CNV, small high-energy laser spots were used to treat several areas of the macula in the retinas of cynomolgus monkeys according to previously published protocols. To prevent abnormalities, bevacizumab (a potent VEGF inhibitor) and adalimumab or ESBA105 (potent TNF-alpha inhibitors) were given by intravitreal injection 1 week before and 1 week and 3 weeks after laser treatment. ESBA105 was also applied topically in a separate group. Control animals were treated with either intravitreal or topical saline. Eyes were monitored by ophthalmic examination, color photography, and fluorescein angiography.
  
  
  RESULTS
  Inhibition of VEGF by bevacizumab completely blocked the formation of CNV. Both TNF-alpha inhibitors also significantly reduced laser-induced CNV abnormalities after intravitreal administration. Most important, topical use of the anti-TNF-alpha single-chain antibody fragment ESBA105 also reduced the formation of CNV.
  
  
  CONCLUSIONS
  TNF-alpha contributes to laser-induced CNV formation, and its inhibition can be a new therapeutic target for CNV. This study suggests TNF-alpha as another therapeutic target for the prevention and treatment of CNV and adds to the emerging clinical data suggesting the therapeutic value of TNF-alpha inhibitors in age-related macular degeneration (AMD). Further, this study shows that topical therapy with suitable antibody fragments has the potential of being introduced to retinal disease treatment regimens.
authors.affiliation: ESBA Tech, an Alcon Biomedical Research Unit, Schlieren, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtlen
authors.forename: Tim T
authors.initials: TT
authors.lastname: Lam
authors.forename: T Michael
authors.initials: TM
authors.lastname: Nork
authors.forename: Tim
authors.initials: T
authors.lastname: Streit
authors.forename: David M
authors.initials: DM
authors.lastname: Urech
mesh_terms: D000068879:Adalimumab; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D056965:Injections, Intraocular; D007834:Lasers / Q000009:adverse effects; D008252:Macaca fascicularis; D012720:Severity of Illness Index; D012965:Sodium Chloride / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014822:Vitreous Body
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C547155:ESBA105; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D012965:Sodium Chloride; D000068879:Adalimumab