Company > 07 - May - 2015

Potential for Optogenetics in Future Vision Therapies


In this issue:

Potential for Optogenetics in Future Vision Therapies

Within neuroscience and related disciplines, the development of the technique known as Optogenetics is widely regarded as one of the most important breakthroughs in modern science. The ability to target certain neuronal populations with light to trigger certain behavior is the broad idea behind this technique. In the past decade, hundreds of research groups have used Optogenetics to learn how various networks of neurons contribute to behavior, perception and cognition. From eating disorders to epilepsy, to Parkinson's disease - the potential of Optogenetic investigations in brain-relation conditions is enormous.

The latest development within Optogenetics is a potential application in visual therapeutics. Researchers at MIT's Media Lab have developed a red-shifted opsin that produces significantly more retinal nerve-cell spiking when exposed to red light than opsins developed in the past. The red-shifted microbial rhodopsin (named 'JAWS') is basically an engineered chloride ion-pump. These are pigments present in the retinal cells of many species that when exposed to light, move positive ions into cells to boost their activity (excitation), or move negative ions into cells to shut them down (inhibition). This phenomenon is known as neural hyper-polarization.

The researchers aimed to study the effects of Optogenetic neural hyper-polarization on mice having retinitis pigmentosa - a visual disorder that results first in night-blindness and then overall blindness as a result of photoreceptor degeneration. A potential therapy for patients with this condition is to re-sensitize the cone cells to light by introducing light-activated ion pumps in the cone photoreceptors. When JAWS was expressed in the retinal cones of retinitis pigmentosa mice, the researchers found photo-stimulation of these receptors to induce more activity in retinal cells than any previously used ion-pump. These studies may prove to be the pathways for curing different forms of blindness in people in the years to come.

The development of JAWS not only has potential in vision therapy but also in noninvasive optogenetic inhibition of neural activity. JAWS has found to be a good inhibitor of stimulus-evoked neural response in the presence of red light. This provides an area of possible research for brain-related conditions where today, surgery is the only option.

As the number of applications of Optogenetic investigations grow, more research is being done to use this technique to identify areas of the brain responsible for specific behavior and functions. While mapping the complete human brain is still years away, every day progress is being made in labs around the world- leading us one step closer to safer treatments for brain disorders and understanding the mysteries of its workings.

Sources:

'Let There Be Light'- Your Future Brain- Scientific American Mind, Nov-Dec 2014, Dr. E Boyden : Online Link- Scientific American Mind

'Noninvasive optical inhibition with a red-shifted microbial rhodopsin'- paper, published Aug 2014- Nature Neuroscience, Amy S Chuong : Online Link- Nature Neuroscience


Optogenetics Enables Neural Control of Spinal Cord

Researchers at MIT have developed highly flexible fiber probes made of polymers for the combined optical stimulation and recording of neural activity in the spinal cords of mice. By using these fiber probes, they were able to observe lower-limb muscle activation by twitches that were closely correlated to laser pulses. This leads to the hypothesis that optical stimulation of the spinal cord leads to activation of moto-neuron fibers. Laserglow's 473 nm Blue laser was used as a light source.

The spinal cord consists of multiple neuron channels that carry motor stimuli from the brain to limbs, and sensory information back from the limbs to the brain via the central nervous system. This 'closed loop' relay of information may be disrupted when injuries happen. Hence, any treatment of these injuries focuses on restoring this closed loop and should be able to both stimulate and record neural activity.

The spinal cord is a complex, fibrous, highly flexible part of the nervous system that undergoes repeated elastic bending in normal motion. The team needed to create a probe that would match its flexibility, without breaking and damaging the tissue. The fabricated fiber probes are able to transmit light with low losses even when the structure is bent. The probes, combined with an optical core for optogenetic stimulation and conductive electrodes for recording neuron activity, were then applied to lumbar spinal cord of transgenic mice expressing a light-sensitive protein - channelrhodopsin-2 (ChR2). Laser pulses delivered through the optical core evoked robust neural activity, which temporarily lead to lower-limb muscle activation.

To ensure the neural activity was only caused by optogenetic activation, the researchers tried the same method on 'normal' mice. The attached electrodes only recorded neural activity based on sensory inputs or external stimuli. But no activity could be attributed to optical input.

The researchers believe that this study provides a stepping stone towards understanding how motor and sensory functions can be restored in patients suffering from paralysis. The study was published in Volume 24, Issue 42 of 'Advanced Functional Materials' in Nov 2014. To read more about the experiment, go to: Wiley Online Full Paper


Holographic Bio-imaging May Enhance Cellular-Level Surgery

Scientists at the Korea Advanced Institute of Science and Technology (KAIST) have developed a new method to locate and move microscopic particles, which is more effective compared to previous optical tweezer approaches. Researcher and lead author Kyoohyun Kim believes that this development has potential to greatly improve the quality of observation and measurement in cellular-level surgeries, by displaying real-time 3D images of the cell as the surgery (and subsequent recovery) takes place.

Optical tweezers have had a huge impact on Nano-particle physics and Nanotechnology, by enabling scientist to move particles at an atomic level. A traditional Optical tweezer uses a highly focused laser beam to exert force on microscopic particles. An optical microscope is then able to measure the light scattered by such particles and also determine their position in two dimensions. However, this method doesn't allow for locating the precise position of particles along the optical axis. It's made further difficult when the scattered light is distorted by the particles having complicated shapes, or when other particles block the target on the optical axis.

The new method uses Optical Diffraction Tomography (ODT) to overcome these hurdles. ODT is based on the same principle as x-ray imaging (Compound Tomography) used in hospitals. A 3D image is produced by taking several images from various illumination angles.

Prof. YongKeun Park at KAIST believes that this method can be applied in various fields including physics, optics, nanotechnology and medical science.

To learn how the team at KAIST demonstrated the principles of ODT in their research, read more at : Photonics.com full article

Laserglow Technologies is proud to be a supplier of DPSS Lasers to world-renowned labs that perform Optical tweezers based research with near-infrared systems

Additional Resources:

The research was published in Optica (doi: 10.1364/Optica.2.000343

For more information, visit: www.kaist.edu

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