Nature Communications reports: Technion Scientists Develop a New Approach for Artificial Stimulation of Blind Retinas

4Method is based on optogenetics – a newly developing area in neuroscience, and is a first step towards non-invasive sight restoration in cases of degenerative retinal diseases

Scientists from the Faculty of Biomedical Engineering at the Technion developed a novel approach towards non-invasive vision restoration in blind retinas, by combining holography and optogenetics – a rapidly developing field in neuroscience. The study is published in the multidisciplinary Journal, Nature Communications.   

“Degenerative diseases of the outer retina are one of the major causes of blindness in the Western world,” says Professor Shy Shoham. “These diseases are characterized by degeneration of the photoreceptors, which serve as light sensors, while downstream cellular levels in the retina, and specifically the retinal ganglion cells, are relatively well preserved. Artificial stimulation of these neurons constitutes a potential strategy for getting around the damaged retinal nerve cells.  Restoring lost vision to basic functionality levels has become possible recently through invasive surgical insertion of artificial electronic implants that electrically stimulate surviving retina cells, similar to the snail-shaped cochlear implants used to treat the hearing impaired. Our approach is different and attempts to stimulate the surviving retinal cells without the need for direct implants onto the retina, and may eventually make surgery and implants redundant.”

“Our optogenetic approach relies on genetic expression of ion channels that are light sensitive (proteins derived from algae) in the ganglion cells of the retina,” explains Dr. Inna Reutsky-Gefen, who studied the combination of holography and optogenetics and its application to blind retinas during her doctoral thesis under the mentoring of Professor Shoham, and with assistance from additional study co-authors Lior Golan, Dr. Nairouz Farah, Adi Schejter, Limor Tsur, and Dr. Inbar Brosh. “The ganglion cells are natively transparent and not light-responsive, but after expressing the channel, transform into light-sensors and may be capable of substituting the function of the photoreceptors. In order to create a coherent visual perception in the brain, we have to be able to activate a large number of neurons simultaneously, just as it works in normal visual processing. In addition, this needs to be achieved with high temporal and spatial precision in order to imitate normal retinal information processing. Our study findings demonstrate that optical stimulation of these cells, with the use of a unique holographic projector, enables simultaneous stimulation of a large group of cells with spatial precision at the level of single retinal cells, which is not possible with electrical stimulation. In this manner we demonstrated, in principle, the first ever holographic photo-stimulation capable of restoring cellular activity similar to intact retinal behavior, as a basis for sight rehabilitation developments.”

The holographic projection method developed in the study uses diffractive spatial light modulation to generate images at the focal plane. This approach is light-efficient and does not ”throw away” much of the light energy. The researchers emphasize that this efficiency will be particularly useful in more advanced phases, where it will be required to miniaturize the system into a portable component of a retinal “prosthetic” system.

“Applications of this approach are not limited to vision restoration,” stresses Professor Shoham. “holographic stimulation strategies can permit flexible control of the activity of large cellular networks which artificially express light-sensitive channels, and pave the way towards new medical devices and scientific tools that can help “break” the brain’s neural code.”

The research was funded by a European Research Council Starting Grant to Prof. Shoham.

Illustration: Conceptual design of a future holographic retinal prosthesis mounted on a pair of glasses. Visual input from miniature video camera/s is converted in real-time into activation laser holograms projected onto genetically photo-sensitized retinal cells (in the back of the eye. Credit: Inna Gefen, Roman Kanevsky and Shy Shoham

Scientists from the Technion and the Paris Descartes University developed an innovative approach to healing rare genetic syndromes

“Ectodermal dysplasia” causes deficiency in skin, hair, and nails, cleft lip and palate, and cloudy corneas that can lead to blindness; seven out of every 10,000 births suffer from one form of this syndrome

Scientists from the Technion and the Paris Descartes University in France, developed an innovative approach to healing “Ectodermal Dysplasia Syndromes,” caused by a genetic mutation in the p63 gene.

“Ectodermal Dysplasia” is a group of rare syndromes that affect different areas in the body. This genetic disease causes congenital deficiencies in the skin, hair and nails, cleft lip and palate, and cloudy corneas that could lead to blindness.

In the current research, a unique cellular model was created that summarizes the major fetal deficiencies associated with this disease.

The Israeli scientist (Dr. Ruby Shalom-Feuerstein from the Ruth and Bruce Rappaport Faculty of Medicine) and his French colleagues (Professor Daniel Aberdam and Dr. Isabelle Petit from the Paris Descartes University), generated a new cellular models for the disease. They have reprogrammed cells collected from patients with these syndromes, in order to transform them into fetal stem cells carrying the mutation. In the second stage of the research, the scientists proved that as opposed to normal fetal stem cells, the fetal cells provided by patients were unable to complete fetal maturation processing of skin tissue and corneal development. Finally, due to a small chemical compound known as PRIMA-APR246, a test tube experiment showed a significant improvement in the functioning of the deficient cells.

“The research shows that the PRIMA-APR246 molecule may be able to advance the renewal of skin and corneal development in patients,” said the scientists. “This chemical compound was recently discovered as a potential drug to treat cancer and even successfully passed phases one and two of clinical testing in Sweden without anticipating adverse affects. This will make it all the more simpler for examining its effects on patients with ectodermal dysplasia.”

“Nonetheless, it is important to take precautions and wait for clinical trials that will at the first stage, check the potential effects of the drug on corneal functioning. These tests will take place in the Hopital St. Louis in Paris,” added the research team.

This study demonstrates the relevancy of the fetal stem cells in the research of genetic diseases in general, and disorders that are related to p63 in particular, and paves the way for future treatments.

“According to our assessments, seven babies from every 10,000 births are born with ectodermal dysplasia, and from these cases, the mutant gene is sometimes undetectable while in others it is the p63 gene, the very gene our research is focused on.”

NTU boosts satellite and space research under new collaboration with the Technion

3Two renowned universities, the Nanyang Technological University (NTU), Singapore, and the Technion-Israel Institute of Technology, inked an agreement on 10 February 2013 to set up a collaborative program in satellite and space research.

The signing of the Memorandum of Understanding will allow for the sharing of resources and enhance opportunities for student and faculty exchange. It also comes at a time where both NTU and the Technion have embarked on plans to launch a Nano satellite over the next five years. Both universities have identified potential areas of research, including the study of electric propulsion systems that maintain the orbit control of a Nano satellite.

The two universities will also participate in each other’s satellite programs – namely the Technion IIT’s Space Autonomous Mission for Swarming and Geolocation Nano satellites (SAMSON) program and NTU’s VELOX program. A student exchange program for undergraduates and postgraduates from both institutions is also in the works.

The Agreement was signed by NTU President, Professor Bertil Andersson, and Technion IIT President, Professor Peretz Lavie at the Technion campus in Haifa, Israel.

“This MoU brings together two established technological universities with similar goals in space and satellite research,” says Professor Andersson.

“The agreement will increase contact and mutual support between students and researchers of Technion and NTU, as well as strengthen exchange opportunities at the two universities”.

“The Technion is delighted to explore yet another collaboration with NTU, one of the leading technological universities in the world, ” says the Technion president, Professor Peretz Lavie.

“Combining the knowledge and talents of our institutes will ensure the high quality and excellence of the scientific and technological leaders in Singapore and Israel”.

Both universities have established programs in space research, with NTU having launched the X-SAT microsatellite in 2011 and the Technion launching its Gurwin-II TechSat microsatellite in 1998.

Above (left to right): Prof’ Bertil Andersson, Prof’ Peretz Lavie, and Prof’ Oded Shmueli, executive vice president for research (Technion)

Not only cats: Researchers from the Technion and the University of Haifa found that aphids (plant lice) almost always land on their feet

2A joint multidisciplinary study conducted by researchers from the University of Haifa (Dr. Moshe Gish and Professor Moshe Inbar from the Department of Evolutionary & Environmental Biology) and the Technion  (Dr. Gal Ribak and Research Professor Daniel Weihs from the Faculty of Aerospace, and the Technion Autonomous Systems Program (TASP)), found that  aphids (known as plant lice), which drop from the host plant as a defensive response to danger, are capable of turning themselves over in mid air to almost always land on their feet. The study, which describes the aerodynamic mechanism and the ecological significance of this phenomenon, was recently published in the Current Biology Journal.

Aphids are tiny sap-sucking insects that dwell on plants. The aphids are nourished by plant sap, feeding on several species of legumes, and many species are known to be among the most destructive insect pests on cultivated plants. When aphids sense danger, most often they choose to escape from the host plant by dropping to the ground. Researchers found that immediately after an aphid abandons its host plant, it carries-out a rotational maneuver in mid-air (similar to that done by cats), so that it lands almost always on the ventral side (i.e. right side up, as oppose to landing on its back), not dependant on the starting orientation from which it fell.  The study showed that Aphids dropping from their host plant in an attempt to escape one of its most deadly predators, the seven-spotted ladybug (Coccinella septempunctata), landed on their ventral side in 95% of cases when the drop was made from the height of 20 centimeters, whereas in cases where the drop was made from heights lower than this, its ability to rotate in mid-air was only slightly affected. A fraction of aphids were capable of pulling off the rotational maneuver in mid-air from heights of only a few centimeters. The researchers used special high-speed digital cameras to document the falling process on speeds above 1,000 frames per second, in order to identify the mechanisms used by the aphids in carrying-out the mid-air rotation. It has become clear that already from the beginning of the drop, aphids raise their back legs (in relation to their bodies) and tilt their long antennas forward, to get into a distinct and stable falling position. The researchers built a mathematical model based on air resistance, which demonstrated that during the fall, when the aphid is in its distinct falling position, aerodynamic forces on its body parts (caused by air resistance) cause the aphid to rotate to the point at which an aerodynamic stability is reached that locks the duration of the fall at a fixed angle, whereby its ventral side and legs are pointed in the direction of the ground. In essence, when the aphid’s body is in its distinct falling position, it forms a type of aerodynamic “roly-poly” stance, whereby every deviation from its being stable (during the fall) is automatically and immediately corrected by air resistance, devoid of any action required by the aphid.

The scientists made additional experiments in order to clarify the benefits of an aphid’s ability to land on its ventral side.  Their finding showed that by landing on the ventral side, aphids will have a better chance of being able to cling onto the lower leaves of its host that they collide with on their fall to the ground. For the aphid, the ground is an extremely dangerous place, as it makes them susceptible to surface predators (such as ants), or death of starvation and dehydration. Although the aphid drops from its host plant to escape from dangers, it deliberately tries to do everything in its power to cling to the lower leaves of its host in order to avoid reaching the ground. A theory proposed by researchers, based on the video coverage, and from conclusions drawn by other experiments, suggests that when an aphid lands on its ventral side, sticky pads on the ends of their feet come in contact with the surface of leaves and consequently allows it to cling tightly onto the leaf and stop it from falling. Nonetheless, if an aphid lands on its side or backside, the sticky pads at the ends of their feet do not come in contact with the surface leaves and consequently, the aphid is spewed from the leaf and continues to fall towards the ground.

The mid-air rotational mechanism is very impressive in its simplicity and efficiency, because it doesn’t require from the aphid to act in any way, apart from moving its legs and antennas to the distinctive falling position. The aphid completes its rotation in a very short period of time – in less than two tenths of a second, a phenomenon that is made possible due to its small size (only a few millimeters). In such small masses, the falling speed of an aphid is relatively very low, while the viscosity of the air highly influences the aerodynamic forces on the body. In such instances, quick body rotation ensues, already at the early stages of falling. In contrast to cats, who, owing to their size are forced into making complex maneuvers to ensure they turn over in time before they land, aphids let air resistance and gravity  do the work for them.

The study highlights the significance of the host plant for the aphids that live off them: even upon being forced to escape for fear of becoming instant prey, its adapted mechanism enables the aphid to cling onto the lower leaves of its host and hold onto them for dear life.

Above: The free falling position of aphids. Aphids raise their back legs up and their antennas forward and up to form a stable aerodynamic falling position ensuring a good landing (on their feet). Illustration by Nick W. Sloff