Modulation of the blood-retina-barrier permeability by focused ultrasound: Computational and experimental approaches

The blood-retina-barrier (BRB) is a critical barrier that protects the retinal neurons. It selectively regulates the permeability of molecules, responds to pathologies, and modulates disease progression. While the BRB prevents harmful molecules from the blood from affecting the neurons and is thus essential for retinal health, it also poses a hurdle for therapeutic agents and impedes treatment. The goals are a non-invasive and well-defined transient increase of the BRB’s permeability by mechanical microscale-induced forces, to visualize the permeability change in real-time, and to computationally model the process for an improved understanding and control of the dynamics of larger molecules passage through the BRB. Our approach combines in vivo animal experiments with computational modeling in silico. The in vivo results are used to continuously and iteratively optimize the COMSOL model. In order to modulate BRB’s permeability, we developed a prototype acoustic lens assembly based on COMSOL simulation calculations for the delivery of ultrasonic pressure waves to targeted regions in the retina under optical guidance by light-based imaging. Our data indicate that lower energy focused ultrasound at a PRFP close to 0.8 MPa rapidly increases the permeability of the retinal vessels in a fashion that can be depicted in a real-time fluorescein angiography.