"Reverse optogenetic" protein might pull back the curtain on epilepsy
We're seeing some significant advances in efforts to leverage light-sensitive proteins to improve human health, a field known as optogenetics, but new research out of Germany flips the script on this emerging technology. Scientists have identified a protein that can be deactivated when exposed to light, which could have implications for our understanding of epilepsy and other neurological diseases.
There are types of cells in the body packed with proteins that are sensitive to light. Optogenetics is a technique that takes genes that code for these light-sensitive proteins and adds them to otherwise regular cells as a way of manipulating their behavior. The hope is to use this as a way to treat all kinds of conditions, from paralysis to chronic pain, and we saw a big breakthrough in May when scientists used optogenetics to partially restore a blind man's vision.
Researchers at Ruhr-Universität Bochum have now uncovered what they call a "reverse optogenetic" tool, in a protein that can be switched off, rather than on, by light exposure. The protein is called Opn7b and is what's known as a G protein-coupled receptor. When active, these proteins hold channels open for ions to flow into cells, and also play a role in their signaling.
What was interesting about Opn7b is that the scientists found it was permanently active, unlike many other G protein-coupled receptors. Not much is known about these "constitutively active" proteins, though scientists believe they are implicated in some neuropsychiatric conditions and night blindness, along with some cancers.
The scientists extracted Opn7b from zebrafish and studied it in detail, finding to their great surprise that it could actually be deactivated with light, which completely shut down the signaling chain in the cells. Next, they genetically modified mice to produce the protein, and used light to switch the protein off. This caused epileptic activity in the mice, which the scientists were able to then intervene in using light and other light-controlled proteins.
The researchers believe that their reverse optogenetic tool can therefore be used to investigate the underlying mechanisms and timescales behind epileptic seizures. Further studies centering on Opn7b could also reveal more about the function of other G protein-coupled receptors and how they influence certain diseases, and how the protein could be used to control certain neural circuits.
The research was published in the journal Nature Communications.
Source: Ruhr-Universität Bochum