Effect of Intravitreal Imatinib on Laser-induced Rat Model of Choroidal Neovascularization

Abstract

Purpose: To evaluate the safety and efficacy of intravitreal injection of a tyrosine kinase inhibitor, directed against platelet-derived growth factor and vascular endothelial growth factor receptors, in a rat model of choroidal neovascularization (CNV).

Methods: Phase I: Fifty-four pigmented rats were divided into six groups. Intravitreal injection of imatinib consisting of 330µg/5µl, 250µg/5µl, 165µg/5µl, 80µg/5µl and 40µg/5µl was performed in the right eye of each rat in groups 1 to 5 respectively. In group 6, 5µl of balanced salt solution (BSS) was injected intravitreally. Electroretinography (ERG) was performed at baseline and at weeks one and four. After euthanizing the animals, the right eyes were enucleated for histologic analysis. Based on the ERG records and histologic results, the maximum safe dose of Imatinib was determined. Phase II: Thirty-one rats were used. Experimental CNV was induced by laser photocoagulation in the right eye of each rat. In 21 rats, the highest safe dose of imatinib determined in phase I was injected intravitreally. BSS was injected in the remaining 10 rats. Fluorescein angiography was performed after 4 weeks; then the rats were euthanized and their right eyes were sent for histopathologic evaluation. Eventually, CNV area in tissue sections was measured using ImageJ software and compared between treatment and control groups.

Results: Phase I: ERG showed no statistically significant difference between Imatinib-injected eyes and the controls. However, histologic analysis disclosed focal retinal atrophic changes in the eyes receiving 165µg, 250µg, and 330µg/5µL of the drug. In the eyes that received 40µg and 80µg/5µL Imatinib, retinal histology was unremarkable and immune-reactivity for glial fibrillary acidic protein was not different from the controls. Maximum safe dose of Imatinib was determined to be 80µg/5µl. Phase II: In fluorescein angiography, there was no significant difference between the treatment and control groups in terms of leakages from CNV. Moreover, CNV area in the treatment group was not statistically different from the controls.

Conclusions: Intravitreal imatinib alone is not effective in inhibition of experimental CNV in a rat model.

Keywords: 453 choroid: neovascularization • 637 pathology: experimental • 561 injection