Methods of inducing photosensitivity by targeting channelrhodopsin-2 and halorhodopsin to subcellular regions of retinal ganglion cells
View Patent ↗The present disclosure provides neuromodulators, nucleic acid encoding thereof, and compositions thereof for endowing visual processing abilities to neuronal cells. The present disclosure further provides a method of restoring light sensitivity to degenerate retinas.
1. A method of inducing photosensitivity and ability to detect edge in a neuronal cell, wherein said neuronal cell is a retinal ganglion cell, comprising:
introducing channelrhodopsin-2 and halorhodopsin into said neuronal cell by targeting channelrhodopsin-2 and halorhodopsin to subcellular regions of said neuronal cell;
wherein said channelrhodopsin-2 is fused to a first targeting element that targets expression of said channelrhodopsin-2 in soma of said neuronal cell, wherein the first targeting element is ankyrin G , wherein said halorhodopsin is fused to a second targeting element that targets expression of said halorhodopsin in dendrites of said neuronal cell, wherein the second targeting element is PSD-95, thereby creating an ON-center neuronal cell comprising center-surround antagonism, or wherein said channelrhodopsin-2 is fused to a first targeting element that targets expression of said channelrhodopsin-2 in dendrites of said neuronal cell, wherein the first targeting element is PSD-95, wherein said halorhodopsin is fused to a second targeting element that targets expression of said halorhodopsin in soma of said neuronal cell, wherein the second targeting element is ankyrin G , thereby creating an OFF-center neuronal cell comprising center-surround antagonism.
2. The method according to claim 1 , wherein said neuronal cell is in a degenerate retina.
3. The method according to claim 2 , wherein said degenerate retina has decreased number of photoreceptors relative to a healthy retina.
4. The method according to claim 1 , wherein said neuronal cell is a mammalian retinal ganglion cell.
5. The method according to claim 4 , wherein said neuronal cell is a human retinal ganglion cell.
6. The method according to claim 4 , wherein said neuronal cell is in a human patient.
7. The method according to claim 1 , wherein the first targeting element that targets expression of said channelrhodopsin-2 in soma of said neuronal cell is ankyrin G and the second targeting element that targets expression of said halorhodopsin in dendrites of said neuronal cell is PSD-95.
8. The method according to claim 1 , wherein the first targeting element that targets expression of said channelrhodopsin-2 in dendrites of said neuronal cell is PSD-95 and the second targeting element that targets expression of said halorhodopsin in soma of said neuronal cell is ankyrin G .