(229w) Computational Modeling of Therapeutic Protein Distribution in the Rabbit Eye

Sight-threatening diseases such as age-related macular degeneration and diabetic retinopathy are currently treated by intravitreal injection of anti-VEGF antibodies drugs. To ensure optimum therapeutic benefits, drug concentration should be within or above certain concentration in target tissues. For this purpose, a computational 3D model based on the anatomically accurate rabbit eye dimensions was developed to simulate spatio-temporal evolution of protein distribution in ocular tissues after intravitreal injection. The model considers the convective-diffusive transport processes along with drug elimination in choroidal sink and episcleral veins. It also includes flow of aqueous humor generated in ciliary body within ocular tissues. Previous studies indicated the high dependence of drug distribution by diffusivity coefficients in vitreous. So in order to obtain accurate picture of drug clearance in different ocular tissues, it is necessary to have the accurate drug transport properties. To do this, apparent diffusion coefficient of fluorescein-conjugated protein in fresh rabbit Retina and choroid-RPE was determined in a custom-built diffusion apparatus. The proteins used in this study---- Avastin, Lucentis, Eylea, lysosoms and BSA--- are of different molecular weight and some of them are commonly used drugs for the treatment of ocular diseases. Fluorescein probes concentration was determined by fluorometry. Diffusion coefficient and mobility of proteins in fresh Rabbit vitreous was estimated using fluorescence recovery after photo-bleaching (FRAP), a microscopy based method. Model validated with experimental data for suprachoridal injection of fluorescein labeled Avastin. Comparison of the result for diffusion coefficient through RPE-choroid, retina and vitreous between different proteins showed that it decreased with increasing size as expected. The model simulation indicates such difference has a significant effect on the clearance pattern inside the eye.