Nowadays, this innovative approach that aims at combining the laws of optics with genetic engineering, is revolutionizing the field of cardiovascular and neurobiological research.
But how does this work?
All organisms from archaebacteria to humans express photoreceptor proteins, called Rhodopsins, which provide them the unique ability to “sense and respond” to blue light.
Optogenetics is often used to control neurons in rats. Here we see how blue light is introduced in the brain and elicits neural activity of the neurons expressing rhodopsins.
There are several types of Rhodopsins, and in particular, in animals, they have the property to elicit a signaling pathway by coupling with G-protein transduction pathways. In this way, a change of potential is induced in the cell, and a biological response of the cell is generated. Interestingly, mechanisms like this are involved in circadian clock regulation in animals, which works by inducing specific changes based on changes in light in the environment.
There are other types of opsins t
hat exist in microbes, which have faster kinetics and can be more easily used for genetic engineering because of their simpler structure.
However, these cells aren’t commonly present in humans and animals. How can we express these proteins inside tissues?
One of the first approaches was using a plasmid, which is a DNA fragment that could be integrated with the genome of the host cell, which would therefore cause the cell to express these opsin proteins. However, there were a few issues with this method: first of all, introducing bacteria may be harmful to the cell, and can be toxic for the organism. Also, this organism may promote an immune response in the host.
Interestingly enough, the expression of these proteins can be induced by a viral vector, which means introducing a virus that can later integrate the gene that expresses the opsin protein in the genome of the cell, and later this protein can be expressed. This approach applies to a variety of tissues and appears to be safer than using a plasmid. In particular, one of the first applications was introduced in the 1990s, when a team of researchers applied this principle to cardiac cells, where a high amount of opsin is required for greater results.
However, as this field is evolving very rapidly, there are always new applications and new ways to reduce risks and enhance the accuracy of the results.
But once these proteins are expressed, what do we do with them?
Here is where optic technology comes in. Researchers use optic fibers to transduce light and to direct it in a specific spot, eliciting a response in the desired cells. This can be applied to neurons, where the ionic currents caused by the opsins can cause great changes in cell function since ion currents are the main way with which neurons pass signals between each other. This technology can be also integrated with luciferase, the enzyme that makes fireflies light up, to eliminate the need of using optic fibers. This field is promising to revolutionize regenerative medicine. In fact, soon we may find a way to regenerate tissues, and maybe even organs using optogenetics!
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