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 method for stimulating a tissue structure comprising light sensitive protein, comprising:
a. selecting a targeted tissue structure to be stimulated using illumination at a first subcutaneous location;
b. providing an implantable light conductor configured to be permanently coupled between the first subcutaneous location 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 conductor to the targeted tissue structure.
2 . The method of claim 1 , wherein selecting the targeted tissue structure to be stimulated comprises imaging the target tissue using a modality selected from the group consisting of: radiography, fluoroscopy, ultrasound, magnetic resonance imaging, computed tomography imaging, and endoscopy.
3 . The method of claim 1 , further comprising providing an extracorporeal light source to direct photons through the implantable light conductor to the targeted tissue structure.
4 . The method of claim 1 , wherein the implantable light conductor has a proximal end at the second location comprising an enlarged light collection surface.
5 . The method of claim 4 , wherein the enlarged light collection surface comprises a wedge-shaped geometry with an entrance facet oriented to capture the extracorporeal photons.
6 . The method 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.
7 . The method of claim 1 , wherein the implantable light conductor comprises a material type selected from the group consisting of: glasses, polymers, crystals.
8 . The method of claim 7 , wherein the implantable light conductor comprises a polymer selected from the group consisting of: poly methyl methacrylate, silicone, polydimethylsiloxane, and copolymers thereof.
9 . The method 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.
10 . The method of claim 9 , wherein the reflective layer comprises material selected from the group consisting of silver, rhodium, aluminum, and gold.
11 . The method 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.
12 . The method of claim 11 , wherein the insulating layer comprises a material selected from the group consisting of: silicon dioxide, aluminum oxide, and magnesium dioxide.
13 . The method 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.
14 . The method of claim 13 , wherein the cladding layer comprises material selected from the group consisting of: fluorinated ethylene propylene, polymethylpentene, and THV fluoropolymer blend.
15 . The method 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.
16 . The method of claim 15 , 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.
17 . The method of claim 1 , further comprising installing a pilot member before insertion of the implantable light conductor, the pilot member configured to assist in preparing the associated tissue for implantation of the implantable light conductor.
18 . The method of claim 17 , wherein the pilot member comprises a cutting tool or dilator.
19 . The method of claim 1 , further comprising providing a delivery conduit defining a lumen therethrough through which the implantable light conductor may be removably coupled.
20 . The method of claim 1 , further comprising providing 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.
21 . The method 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.
22 . The method of claim 21 , wherein the relatively thin layer of tissue has a maximum thickness of between about 100 microns and about 1 millimeter.
23 . The method of claim 1 , wherein the second location is directly extracorporeally accessible.
24 . The method of claim 1 , wherein the tissue structure comprising the light sensitive protein has been genetically modified to encode an opsin protein.
25 . The method of claim 24 , wherein the opsin protein is an inhibitory opsin protein.
26 . The method of claim 25 , 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.
27 . The method of claim 24 , wherein the opsin protein is a stimulatory opsin protein.
28 . The method of claim 25 , wherein the stimulatory opsin protein is selected from the group consisting of: ChR2, C1V1-T, C1V1-TT, CatCh, VChR1-SFO, and ChR2-SFO.