Microbe protein offers hope for blindness

For example, tiny single-celled organisms called microbes have recently generated interest in the neuroscience field. Light-sensitive proteins called opsins are inserted onto the cell surfaces of some microbes such as algae. These opsins convert the detection of light into cellular changes. Neuroscientists discovered that by inserting these same proteins onto the cell surfaces of neurons, neural activity can be controlled using light.

The method of controlling neurons by light, termed optogenetics, has enabled researchers to activate or inhibit different neural classes in the nervous system, thereby helping to reveal the functional roles each neural class plays in behavior and physiology. Optogenetics also offers new hope for the treatment of brain disorders because studies on animal models have shown that brain diseases may be treatable by manipulating dysfunctional circuits via optogenetics. Using optogenetics, scientists have been able to reduce seizures in epilepsy patients, reverse drug addiction and attenuate depression.

Preclinical successes in optogenetics have led to much excitement in the field, and research on the lab bench is currently being translated into human clinical trials. While manipulating human neural circuits is not a new idea, optogenetics offers distinct advantages over previous strategies that use electrical means, including the greater specificity of neural classes it targets, and its tighter control on neural activity.

The first clinical trial for therapy with optogenetics was approved by the U.S. Food and Drug Administration in 2015. The treatment consists of injecting a virus into the eye to express Channelrhodopsin-2 (ChR2), a type of opsin in the retinal neurons of individuals who have a genetic condition called retinitis pigmentosa (RP).

RP causes blindness due to the degeneration of photoreceptors in the eye. Photoreceptors normally detect light input and send this information to neurons called retinal ganglion cells. These ganglion cells then transmit light information to the brain for processing. Thus, by expressing ChR2 in the retina, the surviving retinal ganglion cells will also be able to detect light input in the absence of upstream photoreceptors. The company sponsoring the work, Retrosense Therapeutics, writes on their website that the approach enables clinicians to “install new photoreceptors, restoring vision irrespective of which gene defect is responsible for vision loss.”

Although it is not clear whether this type of strategy can fully restore an individual’s vision, mouse studies have shown that expressing ChR2 in retinal neurons can restore light perception in animals that experienced blindness due to photoreceptor loss. Subsequent studies in non-human primates showed that the strategy was well tolerated and safe.

The first phase of the clinical trial for the treatment, termed RST-001, began in November of last year and will be complete in 2017. If RST-001 is shown to be safe for humans, the treatment will be tested in subsequent phases of the clinical trial to determine its effectiveness. However, the first phase of the clinical trial will provide preliminary results about the treatment’s efficacy.

While it is highly unrealistic that RST-001 will magically allow individuals with RP to see everything again because vision is a highly complex and dynamic neural process, it is possible the treatment may allow RP patients to recover some basic forms of visual perception. Even the ability to recognize large objects would be outstanding progress.