Abstract
BackgroundThis 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).MethodsIn 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.ResultsIn 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).ConclusionsDespite 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.
Highlights
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)
The histopathological features and glial fibrillary acidic protein (GFAP) immune-reactivity were unremarkable in groups D and E as compared to the controls (Table 2; Fig. 1)
In the present study, we found 40 μg of IVI as the maximum safe dose based on the ERG and histological findings
Summary
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). 10 % of AMD patients manifest with the neovascular form of the disease [2]. It has been shown that the vascular endothelial growth factor (VEGF) is the most important cytokine in both physiological and pathological angiogenesis, which leads to the Platelet-derived growth factors (PDGF) as the second important cytokines involved in angiogenesis [6], facilitate the recruitment of pericytes and smooth muscle cells and are essential for maturation and stability of the vasculature [7, 8]. The PDGF receptors (PDGFR) are tyrosine kinases, with PDGFR-β being more extensively expressed in endothelial cells and vascular smooth muscle cells [9,10,11].
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