Intravitreal infliximab and choroidal neovascularization in an animal model.
OBJECTIVE
To determine whether intravitreal infliximab can inhibit the growth of choroidal neovascularization (CNV) in an animal model of age-related macular degeneration.


METHODS
Twenty-four brown Norway rats received 6 argon laser lesions of sufficient power to rupture the Bruch membrane in each eye. The right eye received a single intravitreal infliximab injection of 0.15 mg/mL, 1.5 mg/mL, or 15 mg/mL. The left eye received an injection of balanced saline solution. The animals were then euthanized at day 30, the eyes were enucleated, and the amount of CNV was quantified with digital analysis software.


RESULTS
Intravitreal infliximab inhibited CNV growth in the rat laser-trauma model in a dose-response manner. In the 1.5-mg/mL group, there was an 11% reduction in CNV growth (P = .01). In the 15-mg/mL group, CNV growth was decreased by 68% (P < .001).


CONCLUSIONS
Infliximab can inhibit CNV in a rat laser-trauma model, implicating its target cytokine tumor necrosis factor alpha in the angiogenic stimulus for CNV. Suppression of inflammatory cytokines may prove to be another therapeutic target in the treatment of exudative macular degeneration. Clinical Relevance This study demonstrates in a model of macular degeneration an antiangiogenic effect of intravitreal infliximab, which provides a rationale for future human studies.
Olson
Jeffrey L
JL
Department of Ophthalmology, University of Colorado, 1675 Ursula, Aurora, CO 80045, USA. jeffrey.olson@uchsc.edu
Courtney
R Jackson
RJ
Mandava
Naresh
N
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000517:prevention & control*; D003911:Dextrans; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005451:Fluorescein Angiography; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D000069285:Infliximab; D007267:Injections; D008268:Macular Degeneration / Q000175:diagnosis / Q000517:prevention & control; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D003911:Dextrans; D014409:Tumor Necrosis Factor-alpha; C015219:fluorescein isothiocyanate dextran; D000069285:Infliximab; D016650:Fluorescein-5-isothiocyanate