Optogenetics in Humans?

Just over 10 years ago marks the development of one of the most important tools in recent neuroscience history – optogenetics. To put it simply, optogenetics is the process of using light to activate cells (generally neurons) by implanting light sensitive proteins known as opsins, which will then cause firing of the neuron when activated by light.

Obviously activating neurons is nothing new, scientists have been using electric currents and pharmacological interventions to stimulate neurons for years. But the discovery of optogenetics led to many more exciting prospects; firstly the ability to target specific neurons – something electrical stimulation lacks is spatial sensitivity which can lead to unwanted side effects when neurons other than the target cells are stimulated. Optogenetics also allows for neurons to be activated on a much more sensitive timescale – this is in comparison to drugs which can take from minutes to hours to finish exerting their effects.

Like every new technique optogenetics wasn’t without its problems for the first few years, and many scientists that have attempted to use it have failed. However there has been some pretty incredible science out of this discovery that wouldn’t be unheard of in science fiction, such as the implantation of false memories in mice (original research paper found here), and the ability to reactivate otherwise irretrievable memories (original paper here). Memory is a research area that has particularly benefited from the discovery of optogenetics, as it allows for reversible activation/inactivation of certain brain regions. Reversible being the key word here – much of our initial knowledge on memory came from research using lesions of specific brain areas to examine how this can affect memory, and while lesion research has taught us a vast amount, the ability to reversibly activate/inactivate a specific area of the brain can teach us so much more.

Of course as with any technique, once animal studies using optogenetics started showing success, many began to speculate on the use of optogenetics in humans, however this isn’t without its difficulties. One of the biggest obstacles would be the actual delivery of opsins into the neurons. In animal models we usually use genetic manipulations which are not possible in humans. Viral delivery is another option however this can create problems such as overexpression and could also elicit immune responses as the gene products being delivered would be from other species. We also need to develop methods to measure opsin expression in humans, as generally in animal models this is done post-mortem.

Despite these problems, many believe that one of the most likely clinical applications for optogenetics is Parkinson’s disease. Currently deep brain stimulation can be used to alleviate some of the symptoms of Parkinson’s– this involves electrical stimulation through a small electrode implanted in the brain. However this method has problems with spatial and cell specificity and can therefore lead to the stimulation of healthy brain cells and therefore unwanted side effects. These side effects could be overcome with the use of optogenetics to increase spatial sensitivity. However, one of the major problems concerning this application is that this does not treat the underlying cause of Parkinson’s, only alleviates the symptoms. Other drug treatments treating the symptoms of Parkinson’s have been found to lose effectiveness over time – could this be the same for optogenetics?

Another exciting, and perhaps more feasible application of optogenetics is in the treatment of blindness in humans. In fact clinical trials have now been approved in humans to use optogenetic techniques to help restore photo-sensitivity to those suffering from a form of blindness known as retinitis pigmentosa. The outcome of these clinical trials could prove that as well as tool for studying brain mechanisms in animal models, optogenetic techniques could also hold potential as a therapeutic tool for humans.

Overall I believe that optogenetics as a technique is still in its infancy, and the extent of knowledge to be gained from this tool is yet to be fully realised. Although the use of optogenetics in humans may be overly optimistic, there’s no denying that it’s a fascinating tool that has changed the face of neuroscience research.

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