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 illuminating a targeted tissue structure of a patient comprising light sensitive protein, comprising:
an implantable optical applicator configured to deliver light to the targeted tissue structure after implantation in a location adjacent to the targeted tissue structure, the implantable optical applicator operatively coupled to a light source, a controller, a power supply, and an implantable illuminance sensor such that the controller causes the power supply to allow current to flow to the light source to cause an emission of photons to the implantable light actuator based at least in part upon an output signal from the implantable illuminance sensor, wherein the implantable illuminance sensor is positioned such that it captures at least a portion of the photons directed toward the targeted tissue structure by the implantable light applicator.
2 . The system of claim 1 , further comprising an implantable input sensor configured to produce an output signal that is correlated to the illuminance of the implantable optical applicator at a position of photon emission before intersection of such photons with the targeted tissue structure.
3 . The system of claim 1 , wherein the controller is operatively coupled to the implantable input sensor, such that it may compare the output signal from both the implantable input sensor and the implantable illuminance sensor to determine whether unexpected losses are being experienced.
4 . The system of claim 3 , wherein the controller is configured to react a loss level that is past a predetermined threshold loss level.
5 . The system of claim 4 , wherein the controller is configured to react by flagging the event on the loss level being past the predetermined level in a software log file maintained by the controller.
6 . The system of claim 4 , wherein the controller is configured to stop causing the power supply to allow current to flow to the light source.
7 . The system of claim 1 , wherein the implantable illuminance sensor is selected from the group consisting of: a photovoltaic cell, a photodiode, a pyroelectric sensor, a photoresistor, a photoconductor, a phototransistor, and a photogalvanic sensor.
8 . The system of claim 2 , wherein the implantable input sensor is selected from the group consisting of: a photovoltaic cell, a photodiode, a pyroelectric sensor, a photoresistor, a photoconductor, a phototransistor, and a photogalvanic sensor.
9 . The system of claim 2 , further comprising a physiologic sensor configured to produce an output signal that is correlated with a physiologic parameter believed be variable at least in part in response to the input of light to the targeted tissue structure.
10 . The system of claim 9 , wherein the physiologic sensor is selected from the group consisting of: an electromyogram sensor, an electroneurogram sensor, electroencephalogram sensor, an electrocardiogram sensor, a pressure sensor, a temperature sensor, a chemometric sensor, a motion sensor, an accelerometer, a gyro, a strain sensor, an impedance sensor, and a capacitance sensor.
11 . The system of claim 9 , wherein the controller is configured to react to an output of the physiologic sensor being past a certain predetermined threshold.
12 . The system of claim 11 , wherein the controller is configured to react by flagging the event on the loss level being past the predetermined level in a software log file maintained by the controller.
13 . The system of claim 11 , wherein the controller is configured to stop causing the power supply to allow current to flow to the light source.
14 . The system of claim 1 , wherein the implantable optical applicator comprises a cuff configured to at least partially circumferentially surround a portion of the targeted tissue structure.
15 . The system of claim 1 , wherein the implantable optical applicator comprises a slab-type applicator that may be rolled to at least partially circumferentially surround a portion of the targeted tissue structure.
16 . The system of claim 15 , wherein the slab-type applicator is rolled axially to improve engagement of the targeted tissue structure.
17 . The system of claim 15 , wherein the slab-type applicator is rolled longitudinally to improve engagement of the targeted tissue structure.
18 . The system of claim 1 , wherein the implantable optical applicator comprises a helical-type waveguide positioned around the portion of the targeted tissue structure, the helical-type waveguide configured to output couple light inward toward a central longitudinal axis of the helical-type waveguide such that the outcoupled light encounters the targeted tissue structure.
19 . The system of claim 1 , wherein the tissue structure comprising the light sensitive protein has been genetically modified to encode an opsin protein.
20 . The system of claim 19 , wherein the opsin protein is an inhibitory opsin protein.
21 . The system of claim 20 , 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.
22 . The system of claim 19 , wherein the opsin protein is a stimulatory opsin protein.
23 . The system of claim 20 , wherein the stimulatory opsin protein is selected from the group consisting of: ChR2, C1V1-T, C1V1-TT, CatCh, VChR1-SFO, and ChR2-SFO.
24 . The system of claim 1 , wherein the light source is pulsed with a pulse duration between about 0.1 and about 20 milliseconds, using a duty cycle between about 0.1 and 100 percent.
25 . The system of claim 1 , wherein the light source is operated to use the implantable optical applicator to direct photons at the at least one tissue structure with a surface irradiance of between about 5 milliwatts per square millimeter to about 200 milliwatts per square millimeter.