title: Bevacizumab clearance through the iridocorneal angle following intravitreal injection in a rat model.
abstract: Antivascular endothelial growth factor (Anti-VEGF) agents have been widely used for a variety of ocular disorders. The etiology of sustained ocular hypertension following intravitreal administration of anti-VEGF agents is yet to be unraveled. Our study investigates and characterizes the presence of intravitreally injected bevacizumab in the aqueous outflow channels of a rat model. Choroidal neovascularization (CNV) was induced by diode laser photocoagulation to the right eye of twelve Brown Norway rats. Bevacizumab (25 mg/ml) was injected intravitreally after 3 days. Immediately after bevacizumab injection, and 3, 6, 24 and 48 h later, animals were euthanized for immunofluorescence staining. Donkey anti-human IgG labeled with Alexa Fluor(®) 488 was used for bevacizumab immunoreactivity detection. Anti-CD31 antibody was used as a marker for Schlemm's canal endothelial cells. Untreated eyes were used as negative controls. The intensity of the immunostaining was analyzed qualitatively. Bevacizumab immunoreactivity was found in the aqueous outflow channels including the trabecular meshwork and Schlemm's canal immediately after injection, and declined incrementally within the following hours. Forty-eight hours after the injection, no bevacizumab staining was detected in the aqueous outflow channel structures. Our manuscript demonstrates the presence of bevacizumab in the trabecular meshwork and Schlemm's canal structures after intravitreal injection in a CNV induced rat model. Bevacizumab molecules passed through the aqueous outflow channels within 48 h after intravitreal bevacizumab injection.
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel. Electronic address: wataya@gmail.com.
authors.forename: Orly
authors.initials: O
authors.lastname: Gal-Or
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel. Electronic address: docdotan@gmail.com.
authors.forename: Assaf
authors.initials: A
authors.lastname: Dotan
authors.affiliation: Eye Research Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, Israel. Electronic address: mor.dachbash@gmail.com.
authors.forename: Mor
authors.initials: M
authors.lastname: Dachbash
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel. Electronic address: kfirtal@gmail.com.
authors.forename: Kfir
authors.initials: K
authors.lastname: Tal
authors.affiliation: Eye Research Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, Israel. Electronic address: ynisgav@gmail.com.
authors.forename: Yael
authors.initials: Y
authors.lastname: Nisgav
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel; Eye Research Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: dwin@clalit.org.il.
authors.forename: Dov
authors.initials: D
authors.lastname: Weinberger
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ritaehrlich@gmail.com.
authors.forename: Rita
authors.initials: R
authors.lastname: Ehrlich
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel; Eye Research Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: tami.livnat@sheba.health.gov.il.
authors.forename: Tami
authors.initials: T
authors.lastname: Livnat
mesh_terms: D020533:Angiogenesis Inhibitors / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism; D000068258:Bevacizumab / Q000032:analysis / Q000493:pharmacokinetics*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D003315:Cornea / Q000378:metabolism*; D004195:Disease Models, Animal; D058449:Intravitreal Injections; D007498:Iris / Q000378:metabolism*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors; D014129:Trabecular Meshwork / Q000737:chemistry / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Bevacizumab; Clearance; Intraocular pressure; Schlemm's canal; Trabecular meshwork