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 illuminating a targeted tissue structure of a patient comprising light sensitive protein, comprising:
a. providing an implantable optical applicator configured to deliver light to the targeted tissue structure after implantation in a location adjacent to the targeted tissue structure; and
b. operatively coupling the implantable optical applicator 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 method of claim 1 , further comprising providing 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 method of claim 1 , further comprising operatively coupling the controller 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 method of claim 3 , further comprising configuring the controller to react a loss level that is past a predetermined threshold loss level.
5 . The method of claim 4 , further comprising configuring the controller 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 method of claim 4 , further comprising configuring the controller to stop causing the power supply to allow current to flow to the light source.
7 . The method 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 method 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 method of claim 2 , further comprising providing 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 method 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 method of claim 9 , further comprising configuring the controller to react to an output of the physiologic sensor being past a certain predetermined threshold.
12 . The method of claim 11 , further comprising configuring the controller 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 method of claim 11 , further comprising configuring the controller to stop causing the power supply to allow current to flow to the light source.
14 . The method 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 method 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 method of claim 15 , further comprising axially rolling the slab-type applicator to improve engagement of the targeted tissue structure.
17 . The method of claim 15 , further comprising longitudinally rolling the slab-type applicator to improve engagement of the targeted tissue structure.
18 . The method 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 method of claim 1 , further comprising genetically modifying the tissue structure comprising the light sensitive protein to encode an opsin protein.
20 . The method of claim 19 , wherein the opsin protein is an inhibitory opsin protein.
21 . The method 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 method of claim 19 , wherein the opsin protein is a stimulatory opsin protein.
23 . The method 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 method of claim 1 , further comprising pulsing the light source with a pulse duration between about 0.1 and about 20 milliseconds, and using a duty cycle between about 0.1 and 100 percent.
25 . The method of claim 1 , further comprising operating the light source 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.