Riddoch syndrome- Blind woman can See objects in Motion

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Neuroscientists at Western University’s Brain and Mind Institute, have confirmed and detailed a rare case of a blind woman able to see objects — but only if in motion.

A team led by neuropsychologist Jody Culham has conducted the most extensive analysis and brain mapping to date of a blind patient, to help understand the remarkable vision of a 48-year-old Scottish woman, Milena Canning.

Canning lost her sight 18 years ago after a respiratory infection and series of strokes. Months after emerging blind from an eight-week coma, she was surprised to see the glint of a sparkly gift bag, like a flash of green lightning.

Then she began to perceive, sporadically, other moving things: her daughter’s ponytail bobbing when she walked, but not her daughter’s face; rain dripping down a window, but nothing beyond the glass; and water swirling down a drain, but not a tub already full with water.

Glaswegian ophthalmologist Gordon Dutton referred Canning to the Brain and Mind Institute in London, Canada, where tests by Culham’s team included functional Magnetic Resonance Imaging (fMRI) to examine the real-time structure and workings of her brain.

They determined Canning has a rare phenomenon called Riddoch syndrome — in which a blind person can consciously see an object if moving but not if stationary.

“She is missing a piece of brain tissue about the size of an apple at the back of her brain — almost her entire occipital lobes, which process vision,” says Culham, a professor in the Department of Psychology and Graduate Program in Neuroscience.

“In Milena’s case, we think the ‘super-highway’ for the visual system reached a dead end. But rather than shutting down her whole visual system, she developed some ‘back roads’ that could bypass the superhighway to bring some vision — especially motion — to other parts of the brain.”

In essence, Canning’s brain is taking unexpected, unconventional detours around damaged pathways.

During the study, Canning was able to recognize the motion, direction, size and speed of balls rolled towards her; and to command her hand to open, intercept and grab them at exactly the right time. She could navigate around chairs.

Yet she inconsistently identified an object’s colour, and was able only half the time to detect whether someone’s hand in front of her showed thumb-up or thumb-down.

“This work may be the richest characterization ever conducted of a single patient’s visual system,” says Culham. “She has shown this very profound recovery of vision, based on her perception of motion.”

The research shows the remarkable plasticity of the human brain in finding work-arounds after catastrophic injuries. And it suggests conventional definitions of ‘sight’ and ‘blindness’ are fuzzier than previously believed.

“Patients like Milena give us a sense of what is possible and, even more importantly, they give us a sense of what visual and cognitive functions go together,” Culham says.

For Canning, the research at BMI helps explain more about what she perceives and how her brain is continuing to change. She is able to navigate around chairs, can see a bright-shirted soccer goalie and can see steam rising from her morning cup of coffee, for example.

“I can’t see like normal people see or like I used to see. The things I’m seeing are really strange. There is something happening and my brain is trying to rewire itself or trying different pathways,” Canning says.

The research is newly published in the journal Neuropsychologia

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Cytomegalovirus triggers long-lasting eye inflammation

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Infection with cytomegalovirus triggers long-lasting eye inflammation and establishes a dormant pool of the virus in the eyes of mice with healthy immune systems, according to new research presented in PLOS Pathogens by Valentina Voigt of the Lions Eye Institute in Western Australia and colleagues.

Cytomegalovirus infects more than half of all adults by the age of 40, but causes symptoms only in people with compromised immune systems. After a person is infected, the virus persists life-long in a dormant state. In people with healthy immune systems, reservoirs of latent cytomegalovirus were thought to exist in tissues such as lung and salivary gland, but recent evidence hints that they may also occur in tissues thought to be protected by the immune system, including the eyes.

To determine whether cytomegalovirus can access the eyes of hosts with healthy immune systems, Voigt and colleagues performed a series of experiments in mice. They infected the animals with a mouse version of cytomegalovirus and used various imaging and molecular techniques to examine the effects of the pathogen on the eye.

The researchers found that cytomegalovirus indeed infected the iris, but not the retina, of the mouse eye. The virus also caused chronic inflammation of the iris and retina that persisted for months; long after the scientists could no longer detect replicating cytomegalovirus in the eye. Latent cytomegalovirus taken from the eyes 70 days post-infection could be reactivated and begin to replicate in a dish.

“Since the mouse model of cytomegalovirus infection faithfully recapitulates most of the pathologies seen in people after infection with human cytomegalovirus, this study represents an important advance in understanding the full impact of this infection, especially in healthy subjects” says study co-author Mariapia Degli-Esposti.

While more research is needed to determine whether these unexpected findings extend to humans, they suggest that researchers and doctors may need to rethink the effects of cytomegalovirus–and, potentially, other viruses–on the eyes. Some eye problems caused by dormant or reactivated cytomegalovirus in people with healthy immune systems may be misdiagnosed, leading to improper treatment that could damage vision.

Treatment for Lazy Eye

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Amblyopia, commonly known as “lazy eye,” is a visual disorder common in children. The symptoms often are low acuity in the affected or “lazy” eye and impaired depth perception. Researchers have long believed that the impaired vision by one eye is a consequence of exaggerated eye dominance that favors the fellow or “good” eye.

Amblyopia typically is treated by patching the fellow eye to strengthen the affected eye with the goal of restoring normal eye dominance. If correction is not achieved prior to the closing of a “critical period” that ends in early adolescence, visual impairments are more difficult to treat, if not permanent.

Research published today, led by Aaron W. McGee, Ph.D., assistant professor in the University of Louisville Department of Anatomical Sciences and Neurobiology, may lead to changes in how amblyopia is treated, particularly in adults. The research shows that eye dominance and visual acuity are controlled by different areas of the brain, and that one can be corrected without correcting the other.

“We unexpectedly discovered that they aren’t related. They’re independent,” McGee said. “It may not be necessary to instill normal eye dominance to correct visual acuity.”

Previously, McGee and fellow researchers identified a gene called ngr1 as essential in closing the critical period. He found that deleting ngr1 in animal models permits the critical period to remain open or to re-open, facilitating recovery of normal eye dominance and visual acuity. However, the relationship between the improved visual acuity and eye dominance was not clear.

Today’s research reports that recovery of eye dominance alone is not sufficient to promote recovery of acuity, and recovery of acuity can occur even if eye dominance remains impaired. McGee and his colleagues found that eye dominance is regulated by the brain’s primary visual cortex, while visual acuity is governed by another area of the brain, the thalamus.

McGee is the senior author on the article, published in Current Biology, (Distinct Circuits for Recovery of Eye Dominance and Acuity in Murine Amblyopia). Co-authors include Céleste-Élise Stephany Ph.D., a graduate student at the University of Southern California at the time of the research and now a postdoctoral fellow at Harvard Medical School, Shenfeng Qiu, Ph.D., assistant professor of the University of Arizona, and others.

The researchers applied tools to selectively delete the ngr1 gene in different areas of the brain. When ngr1 was deleted from the primary visual cortex, normal eye dominance was recovered but acuity remained impaired. When ngr1 was deleted from the thalamus, eye dominance was impaired, but visual acuity recovered to normal.

“Genes that are limiting recovery from amblyopia are working in parts of brain circuitry that previously were not recognized to have a role in improving visual acuity,” McGee said. “This could allow researchers to address acuity directly, without having to restore normal eye dominance.”

Genome surgery for Eye disease

 

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Researchers from Columbia University have developed a new technique for the powerful gene editing tool CRISPR to restore retinal function in mice afflicted by a degenerative retinal disease, retinitis pigmentosa. This is the first time researchers have successfully applied CRISPR technology to a type of inherited disease known as a dominant disorder. This same tool might work in hundreds of diseases, including Huntington’s disease, Marfan syndrome, and corneal dystrophies. Their study was published online today in Ophthalmology, the journal of the American Academy of Ophthalmology.

Stephen H. Tsang, M.D., Ph.D., and his colleagues sought to create a more agile CRISPR tool so it can treat more patients, regardless of their individual genetic profile. Dr. Tsang calls the technique genome surgery because it cuts out the bad gene and replaces it with a normal, functioning gene. Dr. Tsang said he expects human trials to begin in three years.

Genome surgery is coming,” Dr. Tsang said. “Ophthalmology will be the first to see genome surgery before the rest of medicine.”

Retinitis pigmentosa is a group of rare inherited genetic disorders caused by one of more than 70 genes. It involves the breakdown and loss of cells in the retina, the light sensitive tissue that lines the back of the eye. It typically strikes in childhood and progresses slowly, affecting peripheral vision and the ability to see at night. Most will lose much of their sight by early adulthood and become legally blind by age 40. There is no cure. It is estimated to affect roughly 1 in 4,000 people worldwide.

Since it was introduced in 2012, the gene editing technology known as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has revolutionized the speed and scope with which scientists can modify the DNA of living cells. Scientists have used it on a wide range of applications, from engineering plants (seedless tomatoes) to producing animals (extra lean piglets). But as incredible as genome surgery is, CRISPR has some flaws to overcome before it can live up to its hype of curing disease in humans by simply cutting out bad genes and sewing in good ones.

Diseases like autosomal dominant retinitis pigmentosa present a special challenge to researchers. In autosomal dominant disorders, the person inherits only one copy of a mutated gene from their parents and one normal gene on a pair of autosomal chromosomes. So, the challenge for CRISPR-wielding scientists is to edit only the mutant copy without altering the healthy one.

In contrast, people with autosomal recessive disorders inherit two copies of the mutant gene. When two copies of the gene are mutated, treatment involves a more straightforward, one-step approach of simply replacing the defective gene. Currently, there are six pharmaceutical firms pursuing gene therapies for the recessive form of retinitis pigmentosa; none are developing a therapy for the dominant form. But that may change soon.

That’s because Dr. Tsang and colleagues have come up with a better strategy to treat autosomal dominant disease. It allowed them to cut out the old gene and replace it with a good gene, without affecting its normal function. This so called “ablate-and-replace” strategy can be used to develop CRISPR toolsets for all types of mutations that reside in the same gene and is not exclusive for a type of mutation. This is especially helpful when many types of mutations can lead to the same disorder. For example, any one of the 150 mutations in the rhodopsin gene can result in retinitis pigmentosa. Because Dr. Tsang’s technique can be applied in a mutation-independent manner, it represents a faster and less expensive strategy for overcoming the difficulty of treating dominant disorders with genome surgery.

Typically, CRISPR researchers design a short sequence of code called guide RNA that matches the bit they want to replace. They attach the guide RNA to a protein called Cas9, and together they roam the cell’s nucleus until they find a matching piece of DNA. Cas9 unzips the DNA and pushes in the guide RNA. It then snips out the bad code and coaxes the cell to accept the good code, using the cell’s natural gene repair machinery.

Instead of using one guide RNA, Dr. Tsang designed two guide RNAs to treat autosomal dominant retinitis pigmentosa caused by variations in the rhodopsin gene. Rhodopsin is an important therapeutic target because mutations in it cause about 30 percent of autosomal dominant retinitis pigmentosa and 15 percent of all inherited retinal dystrophies.

This technique allowed for a larger deletion of genetic code that permanently destroyed the targeted gene. Dr. Tsang found that using two guide RNAs instead of one increased the chance of disrupting the bad gene from 30 percent to 90 percent. They combined this genome surgery tool with a gene replacement technique using an adeno-associated virus to carry a healthy version of the gene into the retina.

Another advantage is that this technique can be used in non-dividing cells, which means that it could enable gene therapies that focus on nondividing adult cells, such as cells of the eye, brain, or heart. Up until now, CRISPR has been applied more efficiently in dividing cells than non-dividing cells.

Dr. Tsang used an objective vision test to evaluate the mice after treatment to show a significant improvement in retinal function. An electroretinogram is typically used to evaluate retinal health in humans. It tests the health of the retina much like an electrocardiogram (EKG) tests the health of the heart.

Previous CRISPR studies for retinal diseases have relied on a less objective measure that involves evaluating how often the mouse turns its head in the direction of a light source. Dr. Tsang used electroretinography to show that retinal degeneration slowed in treated eyes compared with untreated eyes.

Info: American Academy of Ophthalmology

Space flight-Associated Neuro-ocular Syndrome (SANS)

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Astronauts who spend time aboard the International Space Station return to Earth with changes to the structure of their eyes which could impact their vision. NASA has studied the phenomenon, known as space flight-associated neuro-ocular syndrome (SANS), for several years, and now a University of Houston optometrist has quantified some of the changes using optical coherence tomography imaging, reporting his findings in JAMA Ophthalmology.

“We studied pre-flight and post-flight data from 15 astronauts who had spent time aboard the space station and detected changes in morphology of the eyes,” said Nimesh Patel, assistant professor. All of them had good vision before and after the flight, but many of them had a change in structures of their eyes.

Patel created customized programs to study data from optical coherence tomography, a noninvasive clinical test that offers cross-section pictures of the retina. His algorithms showed that following prolonged space flight, three major changes occur.

“The findings of this study show that in individuals exposed to long-duration microgravity, there is a change in the position of the Bruch membrane opening, an increase in retinal thickness closer to the optic nerve head rim margin, and an increase in the proportion of eyes with choroidal folds,” said Patel.

While some of these changes would be expected in patients with elevated intracranial pressure, there are also significant differences. For example, choroidal folds are not as prevalent in individuals with intracranial hypertension.

Although the exact cause remains unknown, it is hypothesized that the changes seen in astronauts are a result of microgravity-associated orbital and cranial fluid shifts.

Because some astronauts included in the study had previous spaceflight experience, the preflight data was first compared with healthy control subjects before comparisons with postflight scans. “The results of these investigations suggest that, although there may be resolution of structural changes, there could be long-term ocular anatomical changes after extended-duration spaceflight,” said Patel.

He hopes his findings will one day have applications for patient care.

“My hope is one day we can use some of these algorithms we’ve built on patient care,” noting how important NASA astronauts are in helping understand physiological changes.

“They provide us a novel and interesting set of data that helps us build algorithms sensitive enough to detect small changes.”

Patel is also co-investigator with Brandon Macias, senior scientist at KBR Wyle, on the Ocular Health ISS Study involving one-year mission crew members, to determine how fast these ocular changes develop during spaceflight and how long it takes for patients to recover.

A new non-invasive approach to cure Nearsightedness

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Eye glasses and contact lenses are simple solutions; a more permanent one is corneal refractive surgery. But, while vision correction surgery has a relatively high success rate, it is an invasive procedure, subject to post-surgical complications, and in rare cases permanent vision loss. In addition, laser-assisted vision correction surgeries such as laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) still use ablative technology, which can thin and in some cases weaken the cornea.

Columbia Engineering researcher Sinisa Vukelic has developed a new non-invasive approach to permanently correct vision that shows great promise in preclinical models. His method uses a femtosecond oscillator, an ultrafast laser that delivers pulses of very low energy at high repetition rate, for selective and localized alteration of the biochemical and biomechanical properties of corneal tissue. The technique, which changes the tissue’s macroscopic geometry, is non-surgical and has fewer side effects and limitations than those seen in refractive surgeries. For instance, patients with thin corneas, dry eyes, and other abnormalities cannot undergo refractive surgery. The study, which could lead to treatment for myopia, hyperopia, astigmatism, and irregular astigmatism, was published May 14 in Nature Photonics.

“We think our study is the first to use this laser output regimen for noninvasive change of corneal curvature or treatment of other clinical problems,” says Vukelic, who is a lecturer in discipline in the department of mechanical engineering. His method uses a femtosecond oscillator to alter biochemical and biomechanical properties of collagenous tissue without causing cellular damage and tissue disruption. The technique allows for enough power to induce a low-density plasma within the set focal volume but does not convey enough energy to cause damage to the tissue within the treatment region.

“We’ve seen low-density plasma in multi-photo imaging where it’s been considered an undesired side-effect,” Vukelic says. “We were able to transform this side-effect into a viable treatment for enhancing the mechanical properties of collagenous tissues.”

The critical component to Vukelic’s approach is that the induction of low-density plasma causes ionization of water molecules within the cornea. This ionization creates a reactive oxygen species, (a type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell), which in turn interacts with the collagen fibrils to form chemical bonds, or crosslinks. The selective introduction of these crosslinks induces changes in the mechanical properties of the treated corneal tissue.

When his technique is applied to corneal tissue, the crosslinking alters the collagen properties in the treated regions, and this ultimately results in changes in the overall macrostructure of the cornea. The treatment ionizes the target molecules within the cornea while avoiding optical breakdown of the corneal tissue. Because the process is photochemical, it does not disrupt tissue and the induced changes remain stable.

“If we carefully tailor these changes, we can adjust the corneal curvature and thus change the refractive power of the eye,” says Vukelic. “This is a fundamental departure from the mainstream ultrafast laser treatment that is currently applied in both research and clinical settings and relies on the optical breakdown of the target materials and subsequent cavitation bubble formation.”

“Refractive surgery has been around for many years, and although it is a mature technology, the field has been searching for a viable, less invasive alternative for a long time,” says Leejee H. Suh, Miranda Wong Tang Associate Professor of Ophthalmology at the Columbia University Medical Center, who was not involved with the study. “Vukelic’s next-generation modality shows great promise. This could be a major advance in treating a much larger global population and address the myopia pandemic.”

Vukelic’s group is currently building a clinical prototype and plans to start clinical trials by the end of the year. He is also looking to develop a way to predict corneal behavior as a function of laser irradiation, how the cornea might deform if a small circle or an ellipse, for example, were treated. If researchers know how the cornea will behave, they will be able to personalize the treatment — they could scan a patient’s cornea and then use Vukelic’s algorithm to make patient-specific changes to improve his/her vision.

“What’s especially exciting is that our technique is not limited to ocular media — it can be used on other collagen-rich tissues,” Vukelic adds. “We’ve also been working with Professor Gerard Ateshian’s lab to treat early osteoarthritis, and the preliminary results are very, very encouraging. We think our non-invasive approach has the potential to open avenues to treat or repair collagenous tissue without causing tissue damage.”

Information from  ScienceDaily.com

Ketogenic Diet Helps in preventing Optic nerve Degeneration in Glaucoma

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Axons in glaucomatous optic nerve are energy depleted and exhibit chronic metabolic stress. Underlying the metabolic stress are low levels of glucose and monocarboxylate transporters that compromise axon metabolism by limiting substrate availability. Axonal metabolic decline was reversed by upregulating monocarboxylate transporters as a result of placing the animals on a ketogenic diet. Optic nerve mitochondria responded capably to the oxidative phosphorylation necessitated by the diet and showed increased number. These findings indicate the source of metabolic challenge can occur upstream of mitochondrial dysfunction. Importantly, the intervention was successful despite the animals being on the cusp of significant glaucoma progression.

Scientists have known for years that the meticulously portioned diet, which shifts the body’s metabolism into a state mimicking starvation, can protect against neurodegeneration. The diet staves off seizures in some people with drug-resistant epilepsy and has benefited patients with brain trauma, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis.

The new study supports an additional benefit: prolonged maintenance of a ketogenic state may prevent degeneration of the optic nerve head in people with glaucoma.

Information from May 14 report in the Journal of Neuroscience.