In Vivo Analysis to Study Transport Across the Blood-Retinal Barrier

Abstract

We present our detailed, standardized in vivo protocol for the evaluation of influx and efflux transport at the blood-retinal barrier (BRB). Discovering specific transport of drugs and nutrients is essential to improve our understanding of the pharmacological and physiological roles of the BRB. This will contribute to the development of novel systemic drug delivery system that will help with safer and more efficient therapy of severe retinal diseases, such as diabetic retinopathy and age-related macular degeneration. This report describes protocols for analyzing influx transport across the BRB, including integration plot and retinal uptake index (RUI) methods, providing the in vivo influx clearance and RUI value, respectively. In addition, microdialysis, a protocol for analyzing efflux transport across the BRB, provides the apparent first-order rate constant during the terminal phase. Furthermore, in vivo inhibition analyses using RUI and microdialysis provide the data which will help in investigating the involvement of carrier-mediated transport process.