Synthetic azobenzene photoswitches can bypass the degenerated rod and cone photoreceptors of a blind retina and directly photosensitize retinal ganglion cells (RGCs) to restore light-response. This proposal outlines a novel in vivo imaging platform that utilizes 2-photon tracking scanning laser ophthalmoscopy (2P-tSLO) and GCaMP6 Ca2+ imaging to visualize RGCs of blind rd1 mice that have reanimated light sensitivity. The research planned in this fellowship entails 1) the development of an optimized photoswitch delivery system using Ca2+ imaging and multielectrode array electrophysiology and 2) the evaluation of photoswitch light-restoration using in vivo Ca2+ imaging.
This proposal seeks to image the re-animation of light responses in an intact blind retina that has been treated with an azobenzene photoswitch. The planned research will utilize a combination of Ca2+ imaging and a unique in vivo optical microscopy assay based on scanning laser ophthalmoscopy. These studies will provide insight into a novel method to restore light sensitivity and will establish a new assay to examine the restoration of light- sensitivity in vivo.
