(291e) Ultrasound-Enhanced Intrascleral Delivery of Protein

Protein drugs are emerging as new therapeutics to treat blindness-causing diseases. However, intraocular tissues are difficult to reach and the current method relies on direct injection to the back of the eye. This invasive technique carries the risks of eye inflammation, retinal detachment and cataracts. A non-invasive method to deliver macromolecules to the posterior segment of the eye through the transscleral route is being explored in our lab. Sclera, the white outer coat of the eye, is the first barrier in this path. The diffusional resistance of this layer was found to be temporarily reduced by applying low-intensity ultrasound for a short duration. In an ex vivo model with a rabbit eye, the diffusive permeability of fluorescent albumin into the sclera was enhanced by an order of magnitude. Furthermore, the temporary pathways for transport were closed shortly after the ultrasound application, supporting that the ultrasound modulation of scleral property was reversible. An increased flux of protein molecules into sclera may circumvent the clearance by the blood circulation and enable them to assess the neighboring tissues such as the choroid and the retina. This approach has the potential for delivering proteins and other macromolecules to the intraocular tissues non-invasively.