Potential Benefits
The optogenic approach offers for the future an
enormous potential for basic research, because nerve excitation and silencing
can be performed simply by light with high precision in a reversible manner. As
has been already demonstrated, the microbial rhodopsins are tolerated in the
brain of living mammals without obvious impairments. Therefore research is focused
on neurological diseases, because all the advantages of the light stimulation
contain a promising potential for gene therapy and other benefits.
Cell culture, Network analysis
The optogenetic method provides new opportunities to analyze neural networks. This can be achieved by growing cultured nerve cells on micro or nano patterned substrates. Cells can be stimulated or silenced simply by a light-beam with up to now unknown spatial precision. Only for registration of the light evoked signals electrodes devices are necessary. Results from these experiments are expected to be used for theoretical work on neural nets.
Mapping of the brain and behavior
Immediately after having demonstrated that ChR2 can be used for remote control of neurons, many laboratories started projects for the mapping of the brain in living animals. Excellent work by various groups shows, that the application of the optogenetic methods opens the door in the near future for more detailed studies, which have not been possible with the traditional electrical and optical methods. To name some examples; studies are possible on which certain areas of the brain are stimulated via light pipes. Results are obtained on the movement of whisker of rodents; on the olfactory system where light replaces the ligands, and on the movement of animals after stimulation of the motor cortex.
Gene therapy
In the future gene therapy with the optogenetic tools appears possible. Transduction via Adeno Associated Viruses (AAV) has been performed successfully on the human eye to cure Lebers Congenital Amaurosis, by transduction of cells in the human retina to replace the missing retinal isomerase. In analogy to this, AAV´s could be loaded with the microbial rhodopsins and could be used for gene therapy on the diseases listed below.
Recovery of vision
Experiments on photoreceptor deficient mice have shown that light evokes potentials in the visual cortex after the transduction of the ON bipolar cells with ChR2 in the retina. This indicates that the retina of the animals regained photosensitivity, which is transmitted via the optic nerve to the brain. Trajectories of the movement of the animals in the dark and in the light show clearly an increased activity in the light as it is obtained for wild type animals. It is conceivable that such an approach might be possible for blind humans, suffering e.g. the dry or the wet macular degeneration. However, in order to come to this point many biomedical, biophysical and technical hurdles have to be surmounted. This would be an alternative to the technology, which implants photosensitive chips in the human eye, which is far away from a satisfying treatment.
Parkinson disease, Epilepsy
Besides the application of drugs Parkinson disease (PD) can be treated by Deep Brain Stimulation (DBS). The method consists of the stereotactic application of a metallic bipolar or quadrupole electrode to the nucleus subthalamicus within the brain. With help of the electrodes an oscillating electric field is applied stimulating the neuronal cells. With this approach spectacular results are obtained, which represent a substantial improvement compared to the drug therapy. Because of the geometry of the electrodes a precision of about one millimeter can be achieved. The extracellular stimulation by the electrodes induces not only the required depolarization of cells, but also partially a hyperpolarization, which inactivates cells with unwanted side effects. This means that parts of the target area are not under perfect control.
The optogenetic method is completely different. If successful this approach will lead to an improved treatment of PD: Virus induced transduction of cells with ChR2 allows the activation of the target structure in the brain via appropriate light sources without the side effects. As discussed above the advantages are the cell specificity, high temporal and spatial resolution in the micrometer range, which would open ways for the stimulation of substructures of the nucleus subthalamicus. The latter would give the chance to get a deeper understanding of the cause of this disease.
With respect to Epilepsy similar arguments would hold, because here certain areas in the cortex are affected. One could speculate that optogenetics would attract focus also to other diseases including neuropsychiatric diseases.
To summarize, optogenetics offers great opportunities to for basic research in the neurosciences, as already has been demonstrated by many laboratories worldwide. The biomedical applications, however, hold unpredictable challenges and risks. (Source: http://www.mpg.de/36227/bm06_Optogenetics-basetext.pdf)
Cell culture, Network analysis
The optogenetic method provides new opportunities to analyze neural networks. This can be achieved by growing cultured nerve cells on micro or nano patterned substrates. Cells can be stimulated or silenced simply by a light-beam with up to now unknown spatial precision. Only for registration of the light evoked signals electrodes devices are necessary. Results from these experiments are expected to be used for theoretical work on neural nets.
Mapping of the brain and behavior
Immediately after having demonstrated that ChR2 can be used for remote control of neurons, many laboratories started projects for the mapping of the brain in living animals. Excellent work by various groups shows, that the application of the optogenetic methods opens the door in the near future for more detailed studies, which have not been possible with the traditional electrical and optical methods. To name some examples; studies are possible on which certain areas of the brain are stimulated via light pipes. Results are obtained on the movement of whisker of rodents; on the olfactory system where light replaces the ligands, and on the movement of animals after stimulation of the motor cortex.
Gene therapy
In the future gene therapy with the optogenetic tools appears possible. Transduction via Adeno Associated Viruses (AAV) has been performed successfully on the human eye to cure Lebers Congenital Amaurosis, by transduction of cells in the human retina to replace the missing retinal isomerase. In analogy to this, AAV´s could be loaded with the microbial rhodopsins and could be used for gene therapy on the diseases listed below.
Recovery of vision
Experiments on photoreceptor deficient mice have shown that light evokes potentials in the visual cortex after the transduction of the ON bipolar cells with ChR2 in the retina. This indicates that the retina of the animals regained photosensitivity, which is transmitted via the optic nerve to the brain. Trajectories of the movement of the animals in the dark and in the light show clearly an increased activity in the light as it is obtained for wild type animals. It is conceivable that such an approach might be possible for blind humans, suffering e.g. the dry or the wet macular degeneration. However, in order to come to this point many biomedical, biophysical and technical hurdles have to be surmounted. This would be an alternative to the technology, which implants photosensitive chips in the human eye, which is far away from a satisfying treatment.
Parkinson disease, Epilepsy
Besides the application of drugs Parkinson disease (PD) can be treated by Deep Brain Stimulation (DBS). The method consists of the stereotactic application of a metallic bipolar or quadrupole electrode to the nucleus subthalamicus within the brain. With help of the electrodes an oscillating electric field is applied stimulating the neuronal cells. With this approach spectacular results are obtained, which represent a substantial improvement compared to the drug therapy. Because of the geometry of the electrodes a precision of about one millimeter can be achieved. The extracellular stimulation by the electrodes induces not only the required depolarization of cells, but also partially a hyperpolarization, which inactivates cells with unwanted side effects. This means that parts of the target area are not under perfect control.
The optogenetic method is completely different. If successful this approach will lead to an improved treatment of PD: Virus induced transduction of cells with ChR2 allows the activation of the target structure in the brain via appropriate light sources without the side effects. As discussed above the advantages are the cell specificity, high temporal and spatial resolution in the micrometer range, which would open ways for the stimulation of substructures of the nucleus subthalamicus. The latter would give the chance to get a deeper understanding of the cause of this disease.
With respect to Epilepsy similar arguments would hold, because here certain areas in the cortex are affected. One could speculate that optogenetics would attract focus also to other diseases including neuropsychiatric diseases.
To summarize, optogenetics offers great opportunities to for basic research in the neurosciences, as already has been demonstrated by many laboratories worldwide. The biomedical applications, however, hold unpredictable challenges and risks. (Source: http://www.mpg.de/36227/bm06_Optogenetics-basetext.pdf)