SYSTEM AND METHOD FOR OPTOGENETIC THERAPY
Configurations are described for utilizing light-activated proteins within cell membranes and subcellular regions to assist with medical treatment paradigms, such as hypertension treatment via anatomically specific and temporally precise modulation of renal plexus activity. The invention provides for proteins, nucleic acids, vectors and methods for genetically targeted expression of light-sensitive proteins to specific cells or defined cell populations. In particular the invention provides systems, devices, and methods for millisecond-timescale temporal control of certain cell activities using moderate light intensities, such as the generation or inhibition of electrical spikes in nerve cells and other excitable cells.
1 . A system for stimulating a tissue structure comprising light sensitive protein, comprising:
a. an implantable light conductor configured to be permanently coupled between a first subcutaneous location immediately adjacent the tissue structure and a second location selected such that extracorporeal photons directed toward the second location will be transmitted, at least in part, through the implantable light applicator to the targeted tissue structure; and
b. an extracorporeal light source configured to controllably direct photons into the implantable light conductor at the second location in an amount sufficient to cause a change in the light sensitive protein of the tissue structure based at least in part upon a portion of the directed photons reaching the first subcutaneous location.
2 . The system of claim 1 , wherein the implantable light conductor has a proximal end at the second location comprising an enlarged light collection surface.
3 . The system of claim 2 , wherein the enlarged light collection surface comprises a wedge-shaped geometry with an entrance facet oriented to capture the extracorporeal photons.
4 . The system of claim 1 , wherein the implantable light conductor comprises a waveguide configured to propagate substantially all light that is passed through it via total internal reflection.
5 . The system of claim 1 , wherein the implantable light conductor comprises a material type selected from the group consisting of: glasses, polymers, crystals.
6 . The system of claim 5 , wherein the implantable light conductor comprises a polymer selected from the group consisting of: poly methyl methacrylate, silicone, polydimethylsiloxane, and copolymers thereof.
7 . The system of claim 1 , wherein the implantable light conductor comprises a reflective layer configured to recycle light that escapes total internal reflection as it is being propagated down the implantable light conductor.
8 . The system of claim 7 , wherein the reflective layer comprises material selected from the group consisting of silver, rhodium, aluminum, and gold.
9 . The system of claim 1 , wherein the implantable light conductor is at least partially encapsulated with an insulating layer to protect the implantable light conductor or other layers thereupon from the environment.
10 . The system of claim 9 , wherein the insulating layer comprises a material selected from the group consisting of: silicon dioxide, aluminum oxide, and magnesium dioxide.
11 . The system of claim 1 , wherein the implantable light conductor comprises a cladding layer configured to confine evanescent waves within the implantable light conductor as photons are propagated down the implantable light conductor.
12 . The system of claim 11 , wherein the cladding layer comprises material selected from the group consisting of: fluorinated ethylene propylene, polymethylpentene, and THV fluoropolymer blend.
13 . The system of claim 1 , wherein the implantable light conductor comprises a bioinert layer configured to improve biocompatibility and prevent changes to the refractive properties of the implantable light conductor.
14 . The system of claim 13 , wherein the bioinert layer comprises material selected from the group consisting of: gold, platinum, parylene-C, poly(ethylene glycol), phosphoryl choline, polyethylene oxide polymer, and D-mannitol-terminated alkanethiol.
15 . The system of claim 1 , further comprising an installation pilot member configured to be inserted before insertion of the implantable light conductor.
16 . The system of claim 15 , wherein the pilot member comprises a cutting tool or dilator.
17 . The system of claim 1 , further comprising a delivery conduit defining a lumen therethrough through which the implantable light conductor may be removably coupled.
18 . The system of claim 1 , further comprising an implantable light applicator configured to be coupled to the tissue structure, and also coupled to at least one surface of the implantable light conductor at the first location such that photons travelling through the implantable light conductor may be transferred into the implantable light applicator to be directed into the tissue structure.
19 . The system of claim 1 , wherein the second location is entirely encapsulated by tissue, and wherein the implantable light conductor is configured to receive the photons from the extracorporeal light source through a relatively thin layer of tissue.
20 . The system of claim 19 , wherein the relatively thin layer of tissue has a maximum thickness of between about 100 microns and about 1 millimeter.
21 . The system of claim 1 , wherein the second location is directly extracorporeally accessible.
22 . The system of claim 1 , wherein the tissue structure comprising the light sensitive protein has been genetically modified to encode an opsin protein.
23 . The system of claim 22 , wherein the opsin protein is an inhibitory opsin protein.
24 . The system of claim 23 , wherein the inhibitory opsin protein is selected from the group consisting of: NpHR, eNpHR 1.0, eNpHR 2.0, eNpHR 3.0, Mac, Mac 3.0, Arch, and ArchT.
25 . The system of claim 22 , wherein the opsin protein is a stimulatory opsin protein.
26 . The system of claim 23 , wherein the stimulatory opsin protein is selected from the group consisting of: ChR2, C1V1-T, C1V1-TT, CatCh, VChR1-SFO, and ChR2-SFO.