Dextran-Based Oxygen Nanobubbles For Treating Inner Retinal Hypoxia

Central retinal artery occlusion (CRAO) is an obstruction of the retinal artery carrying oxygen to the cells in the inner retinal layers. This lack of oxygen may result in irreversible loss of sight if not treated within 24-36 h. We propose a dextran-based oxygen nanobubble (DONB) platform for intravitreal delivery of oxygen to rescue the inner retina from such ischemic damage. The size distribution of DONBs was 119.6 +/- 44.9 nm and the zeta (zeta)-potential was -35.54 +/- 10.54 mV. The DONBs were found to be stable in amber vials at 5 +/- 3 degrees C for over 4 months and the formulation was not cytotoxic. The therapeutic efficacy of DONBs was first evaluated in retinal precursor cell lines which showed excellent recovery and then in a hypoxia/reperfusion rat eye model. Oxygen distribution measurements and histology indicated excellent recovery of the ganglion and inner retinal cell layers. Electroretinography exhibited normal retinal function. Our unique approach suggests a promising pathway to treat CRAO, a blinding condition for which no effective treatment exists.