(Image caption: An undated handout picture released by Japan’s Riken research institute and Foundation for Biomedical Research and Innovation, shows a retina sheet prepared from iPS cells of a woman for transplant surgery. Japanese researchers on Friday conducted the world’s first surgery to implant “iPS” stem cells in a human body in a major boost to regenerative medicine, two institutions involved said. — PHOTO: AFP/RIKEN AND FOUNDATION FOR BIOMEDICAL RESEARCH AND INNOVATION. Adapted from: The Straits Times)

Japanese doctors test method for restoring impaired vision

Japanese doctors have successfully carried out the first ever implantation of a retina grown from induced pluripotent stem cells (iPS).

The recipient was a 70-year-old woman suffering from macular degeneration.

The procedure took place Friday at the Institute of Biomedical Research and Innovation in the southern city of Kobe, under the direction of a group of scientists from the Riken Institute.

Researchers extracted skin samples from women to grow iPS cells capable of serving as retinal tissue, which then were used to surgically replace part of the macula, the main photo-receptor layer of the retina.

The scientists said that their priority was not to attempt to restore the patient’s sight, but to determine if there are any unforeseen side effects, such as tumours, arising from the procedure.

According to the researchers, who will study the patient’s evolution over the next four years, since the patient will have already lost most of the cells responsible for vision, a transplant may bring only slight improvement or merely slow down the rate of degeneration.

Macular degeneration is an age-related disease that currently affects about 700,000 people in Japan and is the principal cause of blindness in the world.

A simple eye test for multiple sclerosis

As you step outdoors into the bright sunshine, your pupils automatically contract. Scientists from the Australian Centre of Excellence in Vision Science (ACEVS) based at The Australian National University (ANU) are making use of how this ‘pupil reflex’ is connected to the brain as a potential new way of testing the severity of multiple sclerosis (MS).

Dr Eman Ali and her ACEVS colleagues have used an instrument they are developing to accurately measure the pupil responses of MS patients and have found that the pupils of MS sufferers respond appreciably slower. The finding opens the door to a simple and quick way of tracking the severity of MS over time: the slower the response, the worse the MS.

“Our instrument uses special patterns of flashing lights that the patient looks at for four minutes,” says Professor Ted Maddess, a vision scientist at ANU who is head of the ACEVS team.

“We use infrared cameras to measure light-induced changes in the diameters of both pupils, and with computer tracking we can measure the diameter to within a micrometre 30 times a second.

“We have just published the results of our study of 85 MS patients, and we find that in MS patients the pupil response is about 25 milliseconds slower than in our control group. Although the study is preliminary, we believe the test has good potential in individual patients because it can precisely measure the speed of their response to within a millisecond.

“So instead of an expensive MRI to track the condition, the new method gives an accurate readout after just a few minutes. That quick and easy test might, in the future, allow MS patients to be assessed on the spot and have their medication adjusted accordingly,” he says.

MS is a potentially devastating neurological condition affecting the myelin sheath of nerve fibres, leading to sensory disturbances and muscle weakness. Vision, speech, and walking are most often affected, and pain can occur. Puzzlingly, MS affects different people in different ways, but the condition inexorably gets worse with age and there is currently no cure. Some patients experience acute, inflammatory attacks while others don’t.

“MS is the most common neurological disability in adults, with about 12,000 sufferers in Australia,” says Professor Maddess. “Although it seems to be some sort of immune disorder, its cause is still obscure.

“There are many puzzling aspects to MS, and there are many theories,” he says. “But our main aim in this work was just to find a way of accurately monitoring the progression of the disease, a single measure that relates to the degree of disability. MRI is good for giving insight into the inflammation associated with episodic attacks, but it’s not so good at monitoring the chronic decline that’s always going on.

“If we can use our pupil measurements to monitor the decline, we might be in a better position to adjust medications, which often have unpleasant side-effects.”

The instrument to measure the pupil responses is the same one which has also been shown to be helpful in diagnosing vision loss in glaucoma, diabetes, and age-related macular degeneration. The device was developed by Professor Maddess together with Associate Professor Andrew James and other ACEVS team members. Under the name TrueField, it is being commercially developed by an Australian company, Seeing Machines, which plans to sell it as a multipurpose medical diagnostic instrument.

TrueField has already received American FDA clearance, and Professor Maddess is hopeful it might, after some more research, also find a role in monitoring MS. He believes it has good prospects of reducing the high treatment costs associated with the disease.

The paper by Dr Ali and colleagues, “Pupillary response to sparse multifocal stimuli in multiple sclerosis patients”, is available online in the Multiple Sclerosis Journal.

Research Points to Promising Treatment for Macular Degeneration

Experiments show promising results for a drug that could lead to a lasting treatment for millions of Americans with macular degeneration.

Researchers at the University of North Carolina School of Medicine have published new findings in the hunt for a better treatment for macular degeneration. In studies using mice, a class of drugs known as MDM2 inhibitors proved highly effective at regressing the abnormal blood vessels responsible for the vision loss associated with the disease.

“We believe we may have found an optimized treatment for macular degeneration,” said senior study author Sai Chavala, MD, director of the Laboratory for Retinal Rehabilitation and assistant professor of Ophthalmology and Cell Biology & Physiology at the UNC School of Medicine. “Our hope is that MDM2 inhibitors would reduce the treatment burden on both patients and physicians.”

The research appeared Sept. 9, 2013 in the Journal of Clinical Investigation.

As many as 11 million Americans have some form of macular degeneration, which is the most common cause of central vision loss in the western world. Those with the disease find many daily activities such as driving, reading and watching TV increasingly difficult.

Currently, the best available treatment for macular degeneration is an antibody called anti-VEGF that is injected into the eye. Patients must visit their doctor for a new injection every 4-8 weeks, adding up to significant time and cost.

“The idea is we’d like to have a long-lasting treatment so patients wouldn’t have to receive as many injections,” said Chavala. “That would reduce their overall risk of eye infections, and also potentially lower the economic burden of this condition by reducing treatment costs.” Chavala practices at the Kittner Eye Center at UNC Health Care in Chapel Hill and New Bern.

All patients with age-related macular degeneration start out with the “dry” form of the disease, which can cause blurred vision or blind spots. In about 20 percent of patients, the disease progresses to its “wet” form, in which abnormal blood vessels form in the eye and begin to leak fluid or blood, causing vision loss.

While anti-VEGF works by targeting the growth factors that lead to leaky blood vessels, MDM2 inhibitors target the abnormal blood vessels themselves causing them to regress — potentially leading to a lasting effect.

Chavala and his colleagues investigated the effects of MDM2 inhibitors in cell culture and in a mouse model of macular degeneration. They found that the drug abolishes the problematic blood vessels associated with wet macular degeneration by activating a protein known as p53. “p53 is a master regulator that determines if a cell lives or dies. By activating p53, we can initiate the cell death process in these abnormal blood vessels,” said Chavala.

MDM2 inhibitors also have conceivable advantages over another treatment that is currently being investigated in several clinical trials: the use of low-dose radiation for wet macular degeneration. Radiation works by causing DNA damage in cells leading to an increase in p53 and cell death. MDM2 inhibitors activate p53 without causing DNA damage. Also, MDM2 inhibitors can be given by eye injection, which is advantageous over some forms of radiation treatment that require surgery to administer.

Lab team makes unique contributions to the first bionic eye

The Argus II will help people blinded by the rare hereditary disease retinitis pigmentosa or seniors suffering from severe macular degeneration.

As part of the multi-­institutional Artificial Retina Project, Los Alamos researchers helped develop the first bionic eye. Recently approved by the U.S. Food and Drug Administration, the Argus II will help people blinded by the rare hereditary disease retinitis pigmentosa or seniors suffering from severe macular degeneration—diseases that destroy the light-­sensing cell in the retina. Los Alamos scientists served as the Advanced Concepts team, focusing on fundamental issues and out-­of the box ideas.

Significance of the research

The Argus II operates by using a miniature camera mounted in eyeglasses that captures images and wirelessly sends the information to a microprocessor (worn on a belt) that converts the data to an electronic signal. Pulses from an electrode array against the patient’s retina in the back of the eye stimulate the optic nerve and, ultimately, the brain, which perceives patterns of light corresponding to the electrodes stimulated. Blind individuals can learn to interpret these visual patterns.

Los Alamos research achievements

The Los Alamos team examined how visual information is encoded in the pattern of electrical impulses traveling the optic nerve. The scientists developed better ways to visualize and interpret the resulting neural activity patterns when the retina is stimulated.

Using high-­performance video cameras and near-­infrared illumination, the Los Alamos team imaged tiny changes in the light scattering and birefringence properties of neural tissue that are associated with nerve electrical activity, the retina that were produced by stimulation. The team also advised the consortium on the use of compatible technologies to map the human brain function stimulated by the devices or by normal biological vision.

The Laboratory team developed  theory—supported with experimental data—of how electrical activity of nerve cells produces polarized light signals that were used to image retinal function. They created a computer model of the retina directly predicting the dynamics of retinal neurons firing as function of patterns of stimulation. They also created theoretical models of the response of nerve cells to electrical stimulation, which suggest new strategies to stimulate patterns of neural activity with higher resolution and a greater specificity, useful to a wider range of individuals with visual impairment.

The need to improve the retina and electronics interface was the largest technical recording and stimulating arrays, and developed new techniques for coating electrode arrays that might enable advanced neural interfaces in the future, with many more channels and greater tolerance for the challenging environment of electronics implanted in biological tissue.

About the Artificial Retina Project

The DOE Artificial Retina Project is a multi-­institutional collaborative effort to develop and implant a device containing an array of microelectrodes into the eyes of people blinded by retinal disease. The ultimate goal is to design a device to help restore limited vision that enables reading, unaided mobility and facial recognition.

The 10-­year project involved researchers from DOE national laboratories (Argonne, Lawrence Livermore, Los Alamos, Oak Ridge, and Sandia), universities (Doheny Eye Institute at the University of Southern California, California Institute of Technology, North Carolina State University, University of Utah, and the University of California—Santa Cruz), and private industry (Second Sight Medical Products, Inc.). Members of the Los Alamos artificial retina team include team leader John George and members Garrett Kenyon, Michael Ham, Xin-­cheng Yao, David Rector, Angela Yamauchi, Beth Perry, Benjamin Barrows, Bryan Travis, Andrew Dattelbaum, Jurgen Schmidt, James Maxwell and Karlene Maskaly.

The DOE Office of Science funded the Los Alamos portion of the Artificial Retina Project. Laboratory Directed Research and Development (LDRD), the National Institutes of Health and the National Science Foundation have sponsored different aspects of basic R&D on neuroimaging, computational modeling and analysis of neural function, and materials and fabrication techniques that enabled the Los Alamos role in this project. The work supports the Lab’s Global Security mission area and the Science of Signatures and Information, Science, and Technology science pillars.

Scary Faces Terrify Woman with Unusual Condition

When the 67-year-old woman came to the hospital, she was deeply afraid of two things — the visions of odd-looking faces that appeared hovering before her, and that the hallucinations might mean she was losing her mind.

But this retired teacher wasn’t going crazy, and laboratory tests also ruled out two common culprits of hallucinations — infection and drug interactions.

"She was absolutely terrified by what she was seeing," said Dr. Bharat Kumar, an internal medicine resident at the University of Kentucky who treated the woman. In fact, the patient and her family were so concerned in the days before she came to the hospital, they asked a priest about performing an exorcism, Kumar said.

The woman drew a picture of what she saw. The faces had large teeth, eyes and ears, and a horizontally elongated shape, like a football.

That peculiar shape and the fact that the patient recognized that she was hallucinating (rather than believing the visions to be real) provided two important clues in making a diagnosis, Kumar said. He determined that the woman had condition called Charles Bonnet syndrome.

Patients with the syndrome may see small people and animals, bright moving shapes or distorted faces. These hallucinations are purely visual; no sounds accompany them.

In the woman’s case, the condition developed because she had macular degeneration. Tissue within the retinas of her eyes was deteriorating, and her ability to see was declining.

Charles Bonnet syndrome results from the absence of such sensory input to the brain. “When it expects sensory input and receives nothing, it often creates its own input,” Kumar explained.

The brain isn’t a sophisticated computer that processes information objectively and efficiently, he said. “It’s more of a wibbly-wobbly, messy-guessy ball of goo.”

There is no treatment for the condition, but in many cases the hallucinations stop happening as the brain becomes used to vision loss. Patients who are very frightened might be given anti-psychotic medications, but these drugs have serious side effects and aren’t appropriate for everyone.

The woman was grateful to receive her diagnosis and learn that she was not losing her mind, Kumar said. When he followed up with her three months later, she was still having the hallucinations, but they were happening less often.

A 2010 study showed that 10 to 40 percent of elderly patients with visual impairments may have Charles Bonnet syndrome.

Kumar had never before seen a patient with the condition, although he noted that it may occur more commonly than it is diagnosed. “Patients are often hesitant to say that they see things because they are afraid that they will be called crazy,” he said.

The case report was published online Feb. 25 in the journal Age and Aging.

Why Do Age-Related Macular Degeneration Patients Have Trouble Recognizing Faces?

Abnormalities of eye movement and fixation may contribute to difficulty in perceiving and recognizing faces among older adults with age-related macular degeneration (AMD), suggests a study “Abnormal Fixation in Individuals with AMD when Viewing an Image of a Face” appearing in the January issue of Optometry and Vision Science, official journal of the American Academy of Optometry. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

Unlike people with normal vision focus, those with AMD don’t focus on “internal features” (the eyes, nose and mouth) when looking at the image of a face, according to the study by William Seiple, PhD, and colleagues of Lighthouse International, New York.

When Viewing Famous Face, AMD Patients Focus on External Features

The researchers used a sophisticated technique called optical coherence tomography/scanning laser ophthalmoscopy (OCT-SLO) to examine the interior of the eye in nine patients with AMD. Age-related macular degeneration is the leading cause of vision loss in older adults. It causes gradual destruction of the macula, leading to blurring and loss of central vision.

Previous studies have suggested that people with AMD have difficulty perceiving faces. To evaluate the possible role of abnormal eye movements, Dr Seiple and colleagues used the OCT-SLO equipment to make microscopic movies of the interior of the eye (fundus, including the retina and macula) as the patients viewed one of the world’s most famous faces: the Mona Lisa.

This technique allowed the researchers to record eye movements and where the patients looked (fixations) while looking at the face. They compared the findings in AMD patients to a control group of subjects with normal vision.

The results showed significant differences in eye movement patterns and fixations between groups. The AMD patients had fewer fixations on the internal features of the Mona Lisa’s face—eyes, nose, and mouth. For controls, an average of 87 percent of fixations were on internal features, compared to only 13 percent on external features. In contrast, for AMD patients, 62 percent of fixations were on internal features while 38 percent were on external features.

The normal controls also tended to make fewer and shorter eye movements (called saccades) than AMD patients. The differences between groups did not appear to be related to the blurring of vision associated with AMD.

Some older adults with AMD report difficulties perceiving faces. While the problem in “processing faces” is certainly related to the overall sensory visual loss, the new evidence suggests that specific patterns of eye movement abnormalities may also play a role.

Dr Seiple and colleagues note that “abnormal scanning patterns when viewing faces” have also been found in other conditions associated with difficulties in face perception, including autism, social phobias, and schizophrenia. The authors discuss the possible mechanisms of the abnormal scanning patterns in AMD, involving the complex interplay between the eyes and brain in governing eye movement and interpreting visual information.

A previous study suggested that drawing attention to specific characteristics—such as the internal facial features—may increase fixations on internal features and improve face perception. Dr Seiple and coauthors conclude, “That report gives hope that eye movement control training and training of allocation of attention could improve face perception and eye scanning behavior in individuals with AMD.”

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.