Purchase this article with an account.
Alfred K. Yu, Shawn A. Morales, Krisztina I. Forward, Lynn K. Gordon, David G. Telander; Ocular Safety of Dasatinib in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5357.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Dasatinib is a pharmacological inhibitor of the Src family of kinases. Src is the key kinase regulating focal adhesion kinase (FAK) activation. FAK has an important role in the integrin signaling cascade involved in cell adhesion, migration, and invasion. Expression of some of these integrins has been found to be involved in retinal disease. The purpose of this study was to determine if Dasatinib is toxic in the rabbit eye after intraocular injection. Toxicity of Dasatinib was assessed for its potential therapeutic use in retinal disease.
Eight New Zealand Albino rabbits were placed in four treatment groups (2 animals each) receiving dosages of 300nM, 450nM, 600nM, and 900nM of Dasatinib. Rabbits were anesthetized using ketamine hydrochloride (50 mg/kg), xylazine (5 mg/kg), and acepromazine (0.5 mg/kg) administered subcutaneously 15 minutes before the procedure. One drop each of 1% tropicamide and 2.5% phenylephrine hydrochloride was applied topically to achieve pupillary dilation. One drop of proparacaine 0.5% was instilled in each eye before treatment to act as an anesthetic. Rabbits received a dose of Dasatinib intraocularly every week for 6 weeks. Rabbits underwent an indirect ophthalmoscopy examine before each injection. Electroretinogram (ERG) was performed at week 1 and week 4. Rabbits were dark adapted for 1 hour prior to ERG. After rabbits were euthanized eyes were processed and embedded in paraffin for histological examination.
Upon subjective appraisal of the ERG waveforms, the functional integrity of the retina remained fully intact. When comparing baseline b-wave amplitudes and b-wave amplitudes at 4 weeks there were no significant changes to the b-wave amplitude or the b-wave latency time. This is apparent in both scotopic and photopic ERG responses.
ERG assessment of Dasatinib toxicity revealed that Dasatinib does not alter retinal function. Cone and rod function remained stable. Dasatinib can be a useful therapeutic agent in treating retinal diseases such as proliferative vitreoretinopathy and proliferative diabetic retinopathy.
This PDF is available to Subscribers Only