Totally blind mice get sight back
Totally blind mice have had their sight restored by injections of light-sensing cells into the eye, UK researchers report. The team in Oxford said their studies closely resemble the treatments that would be needed in people with degenerative eye disease. Similar results have already been achieved with night-blind mice.
Experts said the field was advancing rapidly, but there were still questions about the quality of vision restored. Patients with retinitis pigmentosa gradually lose light-sensing cells from the retina and can become blind. The research team, at the University of Oxford, used mice with a complete lack of light-sensing photoreceptor cells in their retinas. The mice were unable to tell the difference between light and dark.
Reconstruction
They injected “precursor” cells which will develop into the building blocks of a retina once inside the eye. Two weeks after the injections a retina had formed, according to the findings presented in the Proceedings of the National Academy of Sciences journal. Prof Robert MacLaren said: “We have recreated the whole structure, basically it’s the first proof that you can take a completely blind mouse, put the cells in and reconstruct the entire light-sensitive layer.”
Previous studies have achieved similar results with mice that had a partially degenerated retina. Prof MacLaren said this was like “restoring a whole computer screen rather than repairing individual pixels”. The mice were tested to see if they fled being in a bright area, if their pupils constricted in response to light and had their brain scanned to see if visual information was being processed by the mind.
Vision
Prof Pete Coffee, from the Institute of Ophthalmology at University College London, said the findings were important as they looked at the “most clinically relevant and severe case” of blindness. “This is probably what you would need to do to restore sight in a patient that has lost their vision,” he said.
However, he said this and similar studies needed to show how good the recovered vision was as brain scans and tests of light sensitivity were not enough. He said: “Can they tell the difference between a nasty animal and something to eat?”
Prof Robin Ali published research in the journal Nature showing that transplanting cells could restore vision in night-blind mice and then showed the same technique worked in a range of mice with degenerated retinas. He said: “These papers demonstrate that it is possible to transplant photoreceptor cells into a range of mice even with a severe level of degeneration. “I think it’s great that another group is showing the utility of photoreceptor transplantation.”
Researchers are already trialling human embryonic stem cells, at Moorfields Eye Hospital, in patients with Stargardt’s disease. Early results suggest the technique is safe but reliable results will take several years.
Retinal chips or bionic eyes are also being trailed in patients with retinitis pigmentosa.
Filed under retina light-sensing cells retinitis pigmentosa eye disease photoreceptors retinal degeneration neuroscience science
Simple eye scan can reveal extent of Multiple Sclerosis
A simple eye test may offer a fast and easy way to monitor patients with multiple sclerosis (MS), medical experts say in the journal Neurology. Optical Coherence Tomography (OCT) is a scan that measures the thickness of the lining at the back of the eye - the retina. It takes a few minutes per eye and can be performed in a doctor’s surgery.
In a trial involving 164 people with MS, those with thinning of their retina had earlier and more active MS. The team of researchers from the Johns Hopkins University School of Medicine say larger trials with a long follow up are needed to judge how useful the test might be in everyday practice. The latest study tracked the patients’ disease progression over a two-year period.
Unpredictable disease
Multiple sclerosis is an illness that affects the nerves in the brain and spinal cord causing problems with muscle movement, balance and vision. In MS, the protective sheath or layer around nerves, called myelin, comes under attack which, in turn, leaves the nerves open to damage.
There are different types of MS - most people with the condition have the relapsing remitting type where the symptoms come and go over days, weeks or months. Usually after a decade or so, half of patients with this type of MS will develop secondary progressive disease where the symptoms get gradually worse and there are no or very few periods of remission.
Another type of MS is primary progressive disease where symptoms get worse from the outset. There is no cure but treatments can help slow disease progression. It can be difficult for doctors to monitor MS because it has a varied course and can be unpredictable.
Brain scans can reveal inflammation and scarring, but it is not clear how early these changes might occur in the disease and whether they accurately reflect ongoing damage.
Scientists have been looking for additional ways to track MS, and believe OCT may be a contender. OCT measures the thickness of nerve fibres housed in the retina at the back of the eye. Unlike nerve cells in the rest of the brain which are covered with protective myelin, the nerve cells in the retina are bare with no myelin coat. Experts suspect that this means the nerves here will show the earliest signs of MS damage.
The study at Johns Hopkins found that people with MS relapses had much faster thinning of their retina than people with MS who had no relapses. So too did those whose level of disability worsened. Similarly, people with MS who had inflammatory lesions that were visible on brain scans also had faster retinal thinning than those without visible brain lesions. Study author Dr Peter Calabresi said OCT may show how fast MS is progressing.
"As more therapies are developed to slow the progression of MS, testing retinal thinning in the eyes may be helpful in evaluating how effective those therapies are," he added.
In an accompanying editorial in the same medical journal that the research is published in, MS experts Drs Robert Bermel and Matilde Inglese say OCT “holds promise” as an MS test.
(Image courtesy: Boston University Eye Associates, Inc.)
Filed under MS OCT nerve cells retina retinal thinning eye scan neuroscience science
MIT’s Sebastian Seung has turned mapping the neurons of the retina into a social game, all in the name of neuroscience.
The retina is one of the most easily dissectible parts of the neurological system, and easy to isolate, but “looks like garbage,” Seung says, speaking at Wired 2012. “You need to look at under the microscope. It’s such a complicated structure that it’s safe to say that it’s more than just a camera; it’s a computer that performs some of the tasks of visual perception”. To figure that how it performs those tasks requires mapping the “tangles of spaghetti” that are the neuron pathways between the cells of the retina, a small part of the overall quest to understand the machine that is the brain.
Many people, Seung says, are uncomfortable with the idea of the brain being a machine that can be understood as just a collection of parts. “Most people I talk with hear you’re a neuroscientist [and] they ask lots of questions. But in the end the conversation comes around to you not being able to explain how the mind works without invoking the soul,” he says. The brain is so complicated, though, that it’s no surprise that people would think that there must be more to it than just key parts.
To know that, though, requires building “a parts list” like the kind you might get with some popular Swedish furniture, says Seung — “but the parts list of the retina has frustrated neuroscientists for decades”. It currently runs to a hundred types of cell and counting.
The type of cell that Seung is particularly interested in is the J cell, which plays a role in detecting motion — but neuroscientists aren’t sure how. That’s why Seung and his colleagues launched Eyewire, a site where any amateur neuroscientist can log on and scroll through 3D scans of retinal neurons. Users mark out the paths the neurons trace from cell to cell, correcting the guesses the computer might have got incorrect. There’s even an international leaderboard for people to compete with each other for points.
Seung says: “Professional scientists can’t do it alone — we need amateur neuroscientists. It’s important because there are questions that we all care about, like, why don’t our brains work properly? Sometimes there are neurological disorders like Parkinson’s where the brain decays and dies, but in other disorders we don’t know what’s going on. Some have speculated that it’s wired differently, but how can you know if it’s wired differently without mapping the wires?”
(Source: wired.co.uk)
Filed under Sebastian Seung Eyewire connectome retina J cell neuroscience science
The end of a dogma: Bipolar cells generate action potentials
To make information transmission to the brain reliable, the retina first has to “digitize” the image. Until now, it was widely believed that this step takes place in the retinal ganglion cells, the output neurons of the retina. Scientists in the lab of Thomas Euler at the University of Tübingen, the Werner Reichardt Centre for Integrative Neuroscience and the Bernstein Center Tübingen were now able to show that already bipolar cells can generate “digital” signals. At least three types of mouse BC showed clear evidence of fast and stereotypic action potentials, so called “spikes”. These results show that the retina is by no means as well understood as is commonly believed.
The retina in our eyes is not just a sheet of light sensors that – like a camera chip – faithfully transmits patterns of light to the brain. Rather, it performs complex computations, extracting several features from the visual stimuli, e.g., whether the light intensity at a certain place increases or decreases, in which direction a light source moves or whether there is an edge in the image. To transmit this information reliably across the optic nerve - acting as a kind of a cable - to the brain, the retina reformats it into a succession of stereotypic action potentials – it “digitizes” it. Classical textbook knowledge holds that this digital code – similar to the one employed by computers – is applied only in the retina’s ganglion cells, which send the information to the brain. Almost all other cells in the retina were believed to employ graded, analogue signals. But the Tübingen scientists could now show that, in mammals, already the bipolar cells, which are situated right after the photoreceptors within the retinal network, are able to work in a “digital mode” as well.
Using a new experimental technique, Tom Baden and colleagues recorded signals in the synaptic terminals of bipolar cells in the mouse retina. Based on the responses of these cells to simple light stimuli, they were able to separate the neurons into eight different response types. These types closely resembled those expected from physiological and anatomical studies. But surprisingly, the responses of the fastest cell types looked quite different than expected: they were fast, stereotypic and occurred in an all-or-nothing instead of a graded fashion. All these are typical features of action potentials. Such “digital” signals had occasionally been observed in bipolar cells before, but these were believed to be rare exceptional cases. Studies from the past two years on the fish retina had already cast doubt on the long-held belief that BCs do not spike. The new data from Tübingen clearly show that these “digital” signals are systematically generated in certain types of mammalian bipolar cells. Action potentials allow for much faster and temporally more precise signal transmission than graded potentials, thus offering advantages in certain situations. The results from Tübingen call a widely held dogma of neuroscience into question - and open up many new questions.
Filed under bipolar cells retina spikes visual system neuron ganglion cells neuroscience science
Neurobiologists from Heidelberg University’s Centre for Organismal Studies (COS) have gained new insights into how different types of nerve cells are formed in the developing animal. Through specialised microscopes, they were able to follow the development of the neural retina in the eye of living zebrafish embryos. Using high-resolution three-dimensional time-lapse images the researchers simultaneously observed the division of retinal nerve cells and changes in gene expression. This enabled them to gain insights into the way in which the two processes are linked during eye development and how the number and proportion of different cell types are regulated.
A central question in developmental and regenerative neurobiology concerns the growth processes in animal organisms: How does a growing animal control the generation of the right number of each type and subtype of nerve cell in the brain and what is the relationship between these cells? The retina consists of many different kinds of nerve cells, which are well characterised and common to all vertebrates. Thus, the retina is a particularly good model for studying neuronal development. The researchers studied such retinal developmental processes in living organisms using zebrafish embryos, which are completely transparent and grow rapidly outside their mother.
All retinal cells, which are either excitatory or inhibitory, arise from a relatively small number of apparently homogeneous progenitor cells. These progenitors are able to generate all the different retinal cell types. “It is a challenge to understand how each progenitor cell contributes to the correct number and subtype of nerve cells that compose the final retinal network. Our work contributes to the understanding of how different genes orchestrate neuronal diversity along a progenitor cell lineage, that is the number of cell divisions and types of neurons generated”, says Heidelberg researcher Dr. Lucia Poggi.
To tackle this challenge, Dr. Poggi’s team used different lines of transgenic zebrafish, in which fluorescent reporter proteins highlight the expression of different genes in dividing cells. Working in close cooperation with Dr. Patricia Jusuf of the Australian Regenerative Medicine Institute at Monash University, the researchers found that some particular kinds of excitatory and inhibitory nerve cells tend to be lineally related, i.e. they derive from a common progenitor cell. For the first time, 4D recordings permitted an in vivo analysis of how the generation of particular inhibitory cells is regulated through coordination of cell division mode and gene expression within individual retinal progenitors of excitatory nerve cells.
This study has established a model of how cell lineage influences neuronal subtype specification and neuronal circuitry formation in the native environment of the vertebrate brain. The results were published in the Journal of Neuroscience.
(Source: uni-heidelberg.de)
Filed under zebrafish nerve cells eye development 4D recordings retina neuroscience science
Engineering a Photo-Switch for Nerve Cells in the Eye and Brain
Chemists and vision scientists at the University of Illinois at Chicago have designed a light-sensitive molecule that can stimulate a neural response in cells of the retina and brain — a possible first step to overcoming degenerative eye diseases like age-related macular degeneration, or to quieting epileptic seizures.
Their results are reported online in the journal Nature Communications.
Macular degeneration, the leading cause of vision loss in people over 50, is caused by loss of light-sensitive cells in the retina — the rods and cones.
"The rods and cones, which absorb light and initiate visual signals, are the broken link in the chain, even though what we call the ‘inner cells’ of the retina, in many cases, are still potentially capable of function," says David Pepperberg, professor of ophthalmology and visual sciences in the UIC College of Medicine, the principal investigator on the study.
"Our approach is to bypass the lost rods and cones, by making the inner cells responsive to light."
Pepperberg and his colleagues are trying to develop light-sensitive molecules that — when injected into the eye — can find their way to inner retinal cells, attach themselves, and initiate the signal that is sent to the brain.
Filed under vision retina macular degeneration nerve cells brain neuroscience science
Electrical stimulation of the visual cortex may one day give image perception to blind people.
Work presented at the Society for Neuroscience meeting in New Orleans today suggests a way to create a completely new kind of visual prosthetic—one that restores vision by directly activating the brain.
In a poster session, researchers presented results showing how electrical stimulation of the visual cortex can evoke the sensation of simple flashes of light—including spatial information about those flashes.
While other researchers are trying to develop artificial retinas that feed visual signals into existing sensory pathways (see “A Retinal Prosthetic Powered by Light" and "Now I See You" for instance), the team behind the new work, from the Baylor College of Medicine and the University of Texas Health Science Center in Houston, is exploring the possibility of bypassing those routes all together. This could be vital for those whose retinas are unable to receive retinal stimulation.
The researchers used electrodes to stimulate the brains of three patients who were already undergoing brian surgery to treat epilepsy. All three were able to detect bright spots of light, called phosphenes, when certain regions of their brains were stimulated. And, in seven out of eight trials, the patients were able to correctly see the orientation of a phosphene—in one of two orientations, depending on the stimulation they received.
The work builds upon a study published by the same team in Nature Neuroscience this summer. In that study, the researchers defined which areas of the brain produce phosphene perception when patients’ brains were electrically stimulated.
A press release related to the earlier work says that the researchers “plan to conduct a larger patient study and create multiple flashes of light at the same time. Twenty-seven or so simultaneous flashes might allow participants to see the outline of a letter.”
Filed under blindness neuroscience prosthetics retina vision visual perception Neuroscience 2012 science
Using the Eye as a ‘Window Into the Brain’
An inexpensive, five-minute eye scan can accurately assess the amount of brain damage in people with the debilitating autoimmune disorder multiple sclerosis (MS), and offer clues about how quickly the disease is progressing, according to results of two Johns Hopkins studies.
“The eye is the window into the brain and by measuring how healthy the eye is, we can determine how healthy the rest of the brain is,” says Peter A. Calabresi, M.D., a professor of neurology at the Johns Hopkins University School of Medicine, and leader of the studies described in recent issues of The Lancet Neurology and the Archives of Neurology. “Eye scans are not that expensive, are really safe, and are widely used in ophthalmology, and now that we have evidence of their predictive value in MS, we think they are ready for prime time. We should be using this new quantitative tool to learn more about disease progression, including nerve damage and brain atrophy.”
Calabresi and his colleagues used optical coherence tomography (OCT) to scan nerves deep in the back of the eye, applying special software they co-developed that is capable of assessing previously immeasurable layers of the light-sensitive retinal tissue. The scan uses no harmful radiation and is one-tenth the cost of an MRI. The software will soon be widely available commercially.
Filed under MS eye eye scans retina OCT neuroscience science
The Neuronal Organization of the Retina
The mammalian retina consists of neurons of >60 distinct types, each playing a specific role in processing visual images. They are arranged in three main stages. The first decomposes the outputs of the rod and cone photoreceptors into ∼12 parallel information streams. The second connects these streams to specific types of retinal ganglion cells. The third combines bipolar and amacrine cell activity to create the diverse encodings of the visual world—roughly 20 of them—that the retina transmits to the brain. New transformations of the visual input continue to be found: at least half of the encodings sent to the brain (ganglion cell response selectivities) remain to be discovered. This diversity of the retina’s outputs has yet to be incorporated into our understanding of higher visual function.
Filed under mammals vision retina retinal ganglion cells neuroscience psychology science
A sudden and mysterious burst of activity originating in the retina of a developing fetus spurs brain connections that are essential to development of finely-tuned sight, Yale researchers report in the journal Nature. Interference with this spontaneous wave of activity could play a role in neurodevelopmental disorders such as autism, the scientists speculate.
The study in mice is the first to demonstrate in a living animal that this wave of activity spreads throughout large regions of the brain and is crucial to wiring of the visual system. Without the wiring, infants would not be able to distinguish details in their environment.
“If you interfere with this activity, the circuits are all messed up, the wiring details are all wrong,” said Michael Crair, the William Ziegler III Professor of Neurobiology and Professor of Ophthalmology and Visual Science and senior author of the study.
For instance, this activity might allow a newborn human baby to perceive such details as the five fingers attached to her hand or her mother’s face. This wave wires up the visual system so that infants are poised to learn from their environment soon after birth.
The development of animals from a fertilized egg into trillions of intricately connected and specialized cells is the result of a precisely timed expression of genes. However, the Nature paper introduces another necessary factor — a mysterious wave of activity arising in the retina itself that propagates through several regions of the brain. Crair terms this wave an emergent property, or a trait possessed by a complex system that cannot be directly traced to its individual parts. This experiment in living, neonatal mice shows that this wave is crucial to the proper wiring not only of the visual system but other brain areas as well.
Crair said his lab plans to explore whether interruptions of this activity might play a role in neurodevelopmental disorders such as autism or schizophrenia.
(Source: news.yale.edu)
Filed under brain vision neuron neural activity retina developmental disorders neuroscience psychology science
