title: Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment.
abstract: BACKGROUND
  This two-phase experimental study was conducted to determine the maximum safe dose of intravitreal imatinib (IVI) and its inhibitory effect on a rat model of choroidal neovascularization (CNV).
  
  
  METHODS
  In phase I, 60 rats were divided into six groups (A to F); five of which received IVI with concentrations of 330 (A), 250 (B), 165 (C), 80 (D), and 40 (E) µg/5 µl, and the control group (F) received balanced salt solution (BSS). In addition to electroretinography (ERG), routine histopathological analysis and immunohistochemistry for glial fibrillary acidic protein were performed. In phase II, CNV was induced by laser photocoagulation in 25 rats and the animals were divided into two groups. One group received the maximum safe dose of IVI, determined in phase I, and the other received intravitreal BSS. After 4 weeks, the groups were compared in terms of mean scores of fluorescein leakage in fluorescein angiography and the mean CNV areas in histopathological sections.
  
  
  RESULTS
  In phase I, ERG and the histopathological findings revealed retinal toxicity in groups A to D and A to C, respectively; therefore, a dose of 40 µg/5 µl imatinib was specified as the maximum safe dose for phase II. In phase II, late phase fluorescein leakage and the CNV areas were not significantly different between the imatinib-treated eyes and the controls (p = 0.62 and p = 0.5, respectively).
  
  
  CONCLUSIONS
  Despite the safety of IVI with a dose of 40 µg/5 µl, no inhibitory effect on laser-induced CNV was observed. Further studies are required to investigate the possible synergistic effects of Imatinib with conventional anti-CNV drugs.
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Ophthalmic Research Center, No. 23, Boostan 9 St., Pasdaran Ave, Tehran, 16666 Iran.
authors.forename: Homayoun
authors.initials: H
authors.lastname: Nikkhah
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ahmadieh
authors.affiliation: Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ramezani
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Rezaei Kanavi
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Bagher
authors.initials: SB
authors.lastname: Hosseini
authors.affiliation: Department of Drug and Food Control, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Naficeh
authors.initials: N
authors.lastname: Sadeghi
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohsen
authors.initials: SM
authors.lastname: Khandaghy Meybodi
authors.affiliation: Department of Biostatistics and Epidemiology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yaseri
keywords: Choroidal neovascularization; Fluorescein angiography; Imatinib; Platelet derived growth factor; Rat