Safe Dose of Intravitreal Imatinib and Its Effect on Laser-Induced Choroidal Neovascularization: A Rat-Model Experiment Publisher



Nikkhah H^{1, 6} ; Ahmadieh H² ; Ramezani A³ ; Rezaei Kanavi M¹ ; Hosseini SB¹ ; Sadeghi N⁴ ; Khandaghy Meybodi SM² ; Yaseri M⁵ Show Affiliations
Source: International Journal of Retina and Vitreous Published:2015

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. © 2015 Nikkhah et al.