New Gene Test Could Help LASIK Candidates Avoid Certain Complications

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |LASIK

Why are some people bad candidates for LASIK? Because they have a genetic condition called Avellino corneal dystrophy (ACD), which causes the development of white or grayish granular deposits in the cornea.

Normally these spots develop slowly, over many years, causing a gradual clouding of vision. But LASIK surgery can worsen the density of the cloudiness to the point of severely diminished vision.

A new gene test offered by Avellino Laboratory USA may be crucial in identifying people who carry the ACD gene and therefore should not receive LASIK. According to a study that was published in Ophthalmic Epidemiology, one out of every 870 people is at risk of carrying the gene.

Often people with ACD do develop the small white spots in time to be disqualified by their LASIK surgeon. But for those who don’t yet have any spots in their cornea, the Avellino-GENE Detection System (AGDS) Test offers a safe way to discover if they carry the gene.

The AGDS Test involves a cheek swab that is sent to Avellino Lab USA for testing. Results are available in a couple of days. Typically the test costs around $100, though some clinics include it in the overall cost for LASIK surgery. It is not covered by insurance, but people can use their Flex Spending Accounts to pay for it.

Audio Therapy Can Reduce Patient Anxiety During Cataract Surgery

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Posted on 2nd July 2013 by Pacific ClearVision Institute in Cataracts |General

Using an audio therapy known as binaural beats can significantly reduce patients’ anxiety during cataract surgery, research shows. The 141-patient study, conducted in Thailand, is the first of its kind in cataract surgery, which is one of the most frequently performed procedures worldwide, with more than 3 million performed annually in the United States. The research is being presented at the 116th Annual Meeting of the American Academy of Ophthalmology, jointly conducted this year with the Asia-Pacific Academy of Ophthalmology.

Binaural beat audio therapy consists of two tones that are each pitched at a specific, slightly different frequency, with each tone delivered to a separate ear via headphones. The technique evokes alpha-frequency brainwaves, a state that is linked to relaxation and reduced perception of fear and pain. In this study, the researchers combined binaural beats with soothing music and nature soundscapes that included ocean and forest sounds, to provide a pleasant, familiar experience for patients.

The study was conducted using three groups, each consisting of 47 patients, matched for age, gender, cataract type, and other health factors. Patients who listened to a binaural beats-music mix before, during and after the procedure had less anxiety and slower heart rate, compared with the control group patients who do not receive the therapy.

Systolic blood pressure was also significantly reduced in both the binaural beats-music mix patient group and a second patient group who listened to music only. Control group patients heard the usual sounds that occur in a surgical suite. All patients were assessed before and after surgery using the State-Trait Anxiety scale, a standard test used to diagnose anxiety. Their heart rate and blood pressure were also measured before and after surgery.

The research team focused on cataract surgery because it is usually done under local anesthesia, with the patient awake and continuously exposed to unfamiliar, potentially upsetting sounds such as surgical machinery and conversations between the surgeon and staff. Although the procedure is highly effective and safe, patients may be worried about whether their vision and quality of life will be improved or reduced after the surgery. The results were consistent with the finding of previous research on the use of the therapy reducing anxiety in general surgery patients.

“As populations in many parts of the world grow older, it’s increasingly important for ophthalmologists to explore new ways to improve patient care for seniors,” said Pornpattana Vichitvejpaisal, M.D., of Chiang Mai University, Thailand, who led the research. “Our study shows significant emotional and physiological benefits from adding binaural beats to music therapy for cataract surgery patients. This provides a simple, inexpensive way to improve patients’ health outcomes and satisfaction with their care.”

Dr. Vichitvejpaisal referenced one of his study participants who reported that during her first cataract surgery, she was afraid from the moment she entered the surgical suite. Though she’d been told it wouldn’t take long, the surgery seemed to drag on endlessly. Receiving sound therapy during her second surgery dramatically changed her experience from start to finish. She said that she felt very little anxiety, and that the surgery was over before she knew it.

Scientists Help Explain Visual System’s Remarkable Ability to Recognize Complex Objects

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |Retina

How is it possible for a human eye to figure out letters that are twisted and looped in crazy directions, like those in the little security test internet users are often given on websites?

It seems easy to us — the human brain just does it. But the apparent simplicity of this task is an illusion. The task is actually so complex, no one has been able to write computer code that translates these distorted letters the same way that neural networks can. That’s why this test, called a CAPTCHA, is used to distinguish a human response from computer bots that try to steal sensitive information.

Now, a team of neuroscientists at the Salk Institute for Biological Studies has taken on the challenge of exploring how the brain accomplishes this remarkable task. Two studies published within days of each other demonstrate how complex a visual task decoding a CAPTCHA, or any image made of simple and intricate elements, actually is to the brain.

The findings of the two studies, published June 19 in Neuron and June 24 in the Proceedings of the National Academy of Sciences (PNAS), take two important steps forward in understanding vision, and rewrite what was believed to be established science. The results show that what neuroscientists thought they knew about one piece of the puzzle was too simple to be true.

Their deep and detailed research — -involving recordings from hundreds of neurons — -may also have future clinical and practical implications, says the study’s senior co-authors, Salk neuroscientists Tatyana Sharpee and John Reynolds.

“Understanding how the brain creates a visual image can help humans whose brains are malfunctioning in various different ways — -such as people who have lost the ability to see,” says Sharpee, an associate professor in the Computational Neurobiology Laboratory. “One way of solving that problem is to figure out how the brain — -not the eye, but the cortex — – processes information about the world. If you have that code then you can directly stimulate neurons in the cortex and allow people to see.”

Reynolds, a professor in the Systems Neurobiology Laboratory, says an indirect benefit of understanding the way the brain works is the possibility of building computer systems that can act like humans.

“The reason that machines are limited in their capacity to recognize things in the world around us is that we don’t really understand how the brain does it as well as it does,” he says.

The scientists emphasize that these are long-term goals that they are striving to reach, a step at a time.

Integrating parts into wholes

In these studies, Salk neurobiologists sought to figure out how a part of the visual cortex known as area V4 is able to distinguish between different visual stimuli even as the stimuli move around in space. V4 is responsible for an intermediate step in neural processing of images.

“Neurons in the visual system are sensitive to regions of space — – they are like little windows into the world,” says Reynolds. “In the earliest stages of processing, these windows — -known as receptive fields — -are small. They only have access to information within a restricted region of space. Each of these neurons sends brain signals that encode the contents of a little region of space — -they respond to tiny, simple elements of an object such as edge oriented in space, or a little patch of color.”

Neurons in V4 have a larger receptive field that can also compute more complex shapes such as contours. They accomplishes this by integrating inputs from earlier visual areas in the cortex — -that is, areas nearer the retina, which provides the input to the visual system, which have small receptive fields, and sends on that information for higher level processing that allow us to see complex images, such as faces, he says.

Both new studies investigated the issue of translation invariance — – the ability of a neuron to recognize the same stimulus within its receptive field no matter where it is in space, where it happens to fall within the receptive field.

The Neuron paper looked at translation invariance by analyzing the response of 93 individual neurons in V4 to images of lines and shapes like curves, while the PNAS study looked at responses of V4 neurons to natural scenes full of complex contours.

Dogma in the field is that V4 neurons all exhibit translation invariance.

“The accepted understanding is that individuals neurons are tuned to recognize the same stimulus no matter where it was in their receptive field,” says Sharpee.

For example, a neuron might respond to a bit of the curve in the number 5 in a CAPTCHA image, no matter how the 5 is situated within its receptive field. Researchers believed that neuronal translation invariance — -the ability to recognize any stimulus, no matter where it is in space — -increases as an image moves up through the visual processing hierarchy.

“But what both studies show is that there is more to the story,” she says. “There is a trade off between the complexity of the stimulus and the degree to which the cell can recognize it as it moves from place to place.”

A deeper mystery to be solved

The Salk researchers found that neurons that respond to more complicated shapes — -like the curve in 5 or in a rock — – demonstrated decreased translation invariance. “They need that complicated curve to be in a more restricted range for them to detect it and understand its meaning,” Reynolds says. “Cells that prefer that complex shape don’t yet have the capacity to recognize that shape everywhere.”

On the other hand, neurons in V4 tuned to recognize simpler shapes, like a straight line in the number 5, have increased translation invariance. “They don’t care where the stimuli they are tuned to is, as long as it is within their receptive field,” Sharpee says.

“Previous studies of object recognition have assumed that neuronal responses at later stages in visual processing remain the same regardless of basic visual transformations to the object’s image. Our study highlights where this assumption breaks down, and suggests simple mechanisms that could give rise to object selectivity,” says Jude Mitchell, a Salk research scientist who was the senior author on the Neuron paper.

“It is important that results from the two studies are quite compatible with one another, that what we find studying just lines and curves in one first experiment matches what we see when the brain experiences the real world,” says Sharpee, who is well known for developing a computational method to extract neural responses from natural images.

“What this tells us is that there is a deeper mystery here to be solved,” Reynolds says. “We have not figured out how translation invariance is achieved. What we have done is unpacked part of the machinery for achieving integration of parts into wholes.”

Minjoon Kouh, a former postdoctoral fellow at Salk, participated in the PNAS study. Salk postdoctoral researcher Anirvan Nandy and senior staff scientist Jude Mitchell, of the Salk Systems Neurobiology Laboratory, were co-authors of the Neuron paper.

Both studies were funded by grants from the National Institutes of Health (R01EY019493), the McKnight Scholarship and the Ray Thomas Edwards and W. M. Keck Foundations. In addition, the PNAS study received a grant from the Searle Funds. The Neuron study was additionally funded by grants from the Alfred P. Sloan Foundation, the National Institutes of Health (EY0113802), the Gatsby Charitable Foundation and the Schwartz Foundation, and a Pioneer Fund postdoctoral fellowship.

Chemical Nanoengineering: Designing Drugs Controlled by Light

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |Retina

The scientific cooperation between chemists, biotechnologists and physicists from various Catalan institutes, headed by Pau Gorostiza, from the Institute for Bioengineering of Catalonia (IBEC), and Ernest Giralt, from the Institute for Research in Biomedicine (IRB Barcelona), has led to a breakthrough that will favor the development of light-regulated therapeutic molecules.

The “Design, synthesis and structure of peptides and proteins” lab headed by Dr. Giralt, also senior professor at the University of Barcelona and holder of the 2011 Spanish National Research Prize, has synthesized two peptides (small proteins), which, on irradiation with light, change shape, thereby allowing or preventing an specific protein-protein interaction. The association of these two proteins is required for endocytosis, a process by which cells allow molecules to cross the cell membrane and enter. The Italian scientist Laura Nevola, postdoctoral researcher who works in Dr. Giralt’s lab, and Andrés Martín-Quirós, a PhD student with Dr. Gorostiza’s lab, co-authors of the study, have spent four years working on the design of photo-sensitive peptides.

“Photo-sensitive peptides act like traffic lights and can be made to give a green or red light for cell endocytosis. They are powerful tools for cell biology,” explains Dr. Giralt. “These molecules allow us to use focalized light like a magic wand to control biological processes and to study them,” adds the physicist Pau Gorostiza, ICREA professor, and head of the “Nanoprobes and nanoswitches” lab at IBEC.

The researchers highlight the immediate applicability of these molecules to study, for example, in vitro endocytosis in cancer cells -where this process is uncontrolled- which would allow selective inhibition of the proliferation of these cells. Also, they would also allow the study of developmental biology -where cells require endocytosis to change shape and function, processes that are orchestrated with great spatial and temporal precision. In this context, photo-sensitive peptides will allow the manipulation of the complex development of a multicellular organism by means of light patterns. ” In view of the results, we are now working towards a general recipe to design photo-switchable inhibitory peptides that can be used to manipulate other protein-protein interactions inside cells by applying light,” explain the researchers.

Towards optopharmacology or therapeutic molecules regulated by light

“This first breakthrough will allow us to generate the same kind of peptides for chemical-medical applications,” says Giralt. Dr. Gorostiza was the person who came up with the idea of manipulating biological and pharmacological processes through the use of light after spending five years specializing in this field at the University of California in Berkeley. The coordinator of the ERC Starting Grant project “OpticalBullet” and of the ERC Proof of Concept “Theralight”, both involving collaboration with Giralt’s lab, explains that, “the most immediate therapeutic applications we can expect is for diseases affecting superficial tissue such as the skin, the retina and the most external mucosal membranes.”

The modification of biological processes by means of light is leading to the development of cutting-edge tools for biology and medicine and opening up new research fields, such as optopharmacology and optogenetics. The combination of drugs with external devices to control light may contribute to the development of personalized medicine in which treatments can be adapted to each patient, limiting the time given regions are treated, thus markedly reducing unwanted effects.

Improvements in lasers and chemical engineering

To work towards the development of photo-sensitive drugs, we must enhance the photochemical response of the compounds and be able to stimulate them at visible wavelengths. “Prolonged illumination with ultraviolet light is toxic for cells and is therefore a clear limitation as well has having little tissue penetration capacity,” Giralt explains as an example. Furthermore, the photo-conversion of the compounds needs to be improved as does their stability in the dark in order to be able to “on demand, design them in such a way that they relax rapidly when irradiation with light stops or that they “remember” for hours or days the light stimulation received,” adds Gorostiza.

This study has also involved the collaboration of researchers with IRB Barcelona’s Advanced Digital Microscopy Platform, who designed an adhoc programme to be able to qualitatively and quantitatively validate the effects of the peptides inside the cells in real time. Similarly, in the field of biology, the team has been supported by Dr. Artur Llobet’s group at IDIBELL.

A Telescope for Your Eye: New Contact Lens Design May Improve Sight of Patients With Macular Degeneration

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |Retina

Contact lenses correct many people’s eyesight but do nothing to improve the blurry vision of those suffering from age-related macular degeneration (AMD), the leading cause of blindness among older adults in the western world. That’s because simply correcting the eye’s focus cannot restore the central vision lost from a retina damaged by AMD. Now a team of researchers from the United States and Switzerland led by University of California San Diego Professor Joseph Ford has created a slim, telescopic contact lens that can switch between normal and magnified vision. With refinements, the system could offer AMD patients a relatively unobtrusive way to enhance their vision.

The team reports its work in the Optical Society’s (OSA) open-access journal Optics Express.

Visual aids that magnify incoming light help AMD patients see by spreading light around to undamaged parts of the retina. These optical magnifiers can assist patients with a variety of important everyday tasks such as reading, identification of faces, and self-care. But these aids have not gained widespread acceptance because they either use bulky spectacle-mounted telescopes that interfere with social interactions, or micro-telescopes that require surgery to implant into the patient’s eye.

“For a visual aid to be accepted it needs to be highly convenient and unobtrusive,” says co-author Eric Tremblay of the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. A contact lens is an “attractive compromise” between the head-mounted telescopes and surgically implanted micro-telescopes, Tremblay says.

The new lens system developed by Ford’s team uses tightly fitting mirror surfaces to make a telescope that has been integrated into a contact lens just over a millimeter thick. The lens has a dual modality: the center of the lens provides unmagnified vision, while the ring-shaped telescope located at the periphery of the regular contact lens magnifies the view 2.8 times.

To switch back and forth between the magnified view and normal vision, users would wear a pair of liquid crystal glasses originally made for viewing 3-D televisions. These glasses selectively block either the magnifying portion of the contact lens or its unmagnified center. The liquid crystals in the glasses electrically change the orientation of polarized light, allowing light with one orientation or the other to pass through the glasses to the contact lens.

The team tested their design both with computer modeling and by fabricating the lens. They also created a life-sized model eye that they used to capture images through their contact lens-eyeglasses system. In constructing the lens, researchers relied on a robust material commonly used in early contact lenses called polymethyl methacrylate (PMMA). The team needed that robustness because they had to place tiny grooves in the lens to correct for aberrant color caused by the lens’ shape, which is designed to conform to the human eye.

Tests showed that the magnified image quality through the contact lens was clear and provided a much larger field of view than other magnification approaches, but refinements are necessary before this proof-of-concept system could be used by consumers. The researchers report that the grooves used to correct color had the side effect of degrading image quality and contrast. These grooves also made the lens unwearable unless it is surrounded by a smooth, soft “skirt,” something commonly used with rigid contact lenses today. Finally, the robust material they used, PMMA, is not ideal for contact lenses because it is gas-impermeable and limits wear to short periods of time.

The team is currently pursuing a similar design that will still be switchable from normal to telescopic vision, but that will use gas-permeable materials and will correct aberrant color without the need for grooves to bend the light. They say they hope their design will offer improved performance and better sight for people with macular degeneration, at least until a more permanent remedy for AMD is available.

“In the future, it will hopefully be possible to go after the core of the problem with effective treatments or retinal prosthetics,” Tremblay says. “The ideal is really for magnifiers to become unnecessary. Until we get there, however, contact lenses may provide a way to make AMD a little less debilitating.”

Blood Vessels in the Eye Linked With IQ, Cognitive Function

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |Retina

The width of blood vessels in the retina, located at the back of the eye, may indicate brain health years before the onset of dementia and other deficits, according to a new study published in Psychological Science, a journal of the Association for Psychological Science.

Research shows that younger people who score low on intelligence tests, such as IQ, tend to be at higher risk for poorer health and shorter lifespan, but factors like socioeconomic status and health behaviors don’t fully account for the relationship. Psychological scientist Idan Shalev of Duke University and colleagues wondered whether intelligence might serve as a marker indicating the health of the brain, and specifically the health of the system of blood vessels that provides oxygen and nutrients to the brain.

To investigate the potential link between intelligence and brain health, the researchers borrowed a technology from a somewhat unexpected domain: ophthalmology.

Shalev and colleagues used digital retinal imaging, a relatively new and noninvasive method, to gain a window onto vascular conditions in the brain by looking at the small blood vessels of the retina, located at the back of the eye. Retinal blood vessels share similar size, structure, and function with blood vessels in the brain and can provide a way of examining brain health in living humans.

The researchers examined data from participants taking part in the Dunedin Multidisciplinary Health and Development Study, a longitudinal investigation of health and behavior in over 1000 people born between April 1972 and March 1973 in Dunedin, New Zealand.

The results were intriguing.

Having wider retinal venules was linked with lower IQ scores at age 38, even after the researchers accounted for various health, lifestyle, and environmental risk factors that might have played a role.

Individuals who had wider retinal venules showed evidence of general cognitive deficits, with lower scores on numerous measures of neurospsychological functioning, including verbal comprehension, perceptual reasoning, working memory, and executive function.

Surprisingly, the data revealed that people who had wider venules at age 38 also had lower IQ in childhood, a full 25 years earlier.

It’s “remarkable that venular caliber in the eye is related, however modestly, to mental test scores of individuals in their 30s, and even to IQ scores in childhood,” the researchers observe.

The findings suggest that the processes linking vascular health and cognitive functioning begin much earlier than previously assumed, years before the onset of dementia and other age-related declines in brain functioning.

“Digital retinal imaging is a tool that is being used today mainly by eye doctors to study diseases of the eye,” Shalev notes. “But our initial findings indicate that it may be a useful investigative tool for psychological scientists who want to study the link between intelligence and health across the lifespan.”

The current study doesn’t address the specific mechanisms that drive the relationship between retinal vessels and cognitive functioning, but the researchers surmise that it may have to do with oxygen supply to the brain.

“Increasing knowledge about retinal vessels may enable scientists to develop better diagnosis and treatments to increase the levels of oxygen into the brain and by that, to prevent age-related worsening of cognitive abilities,” they conclude.

‘First Bionic Eye’ Retinal Chip for Blind

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |Retina

University Hospitals (UH) Eye Institute will be one of the first medical centers in the United States to offer the Argus® II Retinal Prosthesis System (“Argus II”).

The Argus II is the first and only “bionic eye” to be approved in countries throughout the world, including the U.S. It is used to treat patients with late stage retinitis pigmentosa (RP). Argus II was developed by Second Sight Medical Products, Inc., located near Los Angeles.

In preparation for the launch of Argus II later this year, implanting centers, including UH, will soon begin to accept consultations for patients with RP. UH is one of a select number of medical centers in 12 major markets in the nation, and the only one in Cleveland and the state of Ohio, chosen by Second Sight to offer the Argus II, which received FDA approval earlier this year.

Argus II works by converting video images captured by a miniature camera, housed in the patient’s glasses, into a series of small electrical pulses that are transmitted wirelessly to an array of electrodes on the surface of the retina. These pulses are intended to stimulate the retina’s remaining cells resulting in the corresponding perception of patterns of light in the brain. Patients then learn to interpret these visual patterns thereby regaining some visual function.

“This is a remarkable breakthrough,” said Suber S. Huang, MD, MBA, Director, UH Eye Institute’s Center for Retina and Macular Disease, who also served as the Independent Medical Safety Monitor for clinical trials of the system and gave the summary closing to the FDA Ophthalmic devices panel.

“The system offers a profound benefit for people who are blind from RP and who currently have no therapy available to them. Argus II allows patients to reclaim their independence and improve their lives.”

RP is a rare inherited, degenerative eye disease that often results in profound vision loss to the level of bare light perception or no light perception. It affects nearly 100,000 Americans. Noted Cleveland businessman and professional sports owner Gordon Gund is blind from this disease.

“We are thrilled that several of the nation’s top hospitals will be the first to offer Argus II to patients in the U.S.,” said Brian Mech, Vice President of Business Development, Second Sight. “After an intensive and difficult selection process, these sites were chosen for their cutting-edge approach to medicine and unparalleled commitment to patient care. We are confident that RP patients seeking treatment at these centers will benefit greatly from the best-in-class services these sites provide.”

Argus II had more than 20 years of work in the field, three clinical trials, more than $100 million in public investment by the National Eye Institute, the Department of Energy, and the National Science Foundation, and an additional $100 million in private investment.

Easy and Effective Therapy to Restore Sight: Engineered Virus Will Improve Gene Therapy for Blinding Eye Diseases

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |Retina

Researchers at UC Berkeley have developed an easier and more effective method for inserting genes into eye cells that could greatly expand gene therapy to help restore sight to patients with blinding diseases ranging from inherited defects like retinitis pigmentosa to degenerative illnesses of old age, such as macular degeneration.

Unlike current treatments, the new procedure is quick and surgically non-invasive, and it delivers normal genes to hard-to-reach cells throughout the entire retina.

Over the last six years, several groups have successfully treated people with a rare inherited eye disease by injecting a virus with a normal gene directly into the retina of an eye with a defective gene. Despite the invasive process, the virus with the normal gene was not capable of reaching all the retinal cells that needed fixing.

“Sticking a needle through the retina and injecting the engineered virus behind the retina is a risky surgical procedure,” said David Schaffer, professor of chemical and biomolecular engineering and director of the Berkeley Stem Cell Center at UC Berkeley. “But doctors have no choice, because none of the gene delivery viruses can travel all the way through the back of the eye to reach the photoreceptors — the light sensitive cells that need the therapeutic gene.

“Building upon 14 years of research, we have now created a virus that you just inject into the liquid vitreous humor inside the eye, and it delivers genes to a very difficult-to-reach population of delicate cells in a way that is surgically non-invasive and safe. “It’s a 15-minute procedure, and you can likely go home that day.”

The engineered virus works far better than current therapies in rodent models of two human degenerative eye diseases, and can penetrate photoreceptor cells in monkeys’ eyes, which are like those of humans.

Schaffer said he and his team are now collaborating with physicians to identify the patients most likely to benefit from this gene delivery technique and, after some preclinical development, hope soon to head into clinical trials.

Schaffer and John Flannery, UC Berkeley professor of molecular and cell biology and of optometry, along with colleagues from UC Berkeley’s Helen Wills Neuroscience Institute and the Flaum Eye Institute at the University of Rochester in New York, published the results of their study on June 12 in the journal Science Translational Medicine.

Harnessing a benign virus for gene therapy

Three groups of researchers have successfully restored some sight to more than a dozen people with a rare disease called Leber’s congenital amaurosis, which leads to complete loss of vision in early adulthood. They achieved this by inserting a corrective gene into adeno-associated viruses (AAV), and injecting these common but benign respiratory viruses directly into the retina. The photoreceptor cells take up the viruses and incorporate the functional gene into their chromosomes to make a critical protein that the defective gene could not, rescuing the photoreceptors and restoring sight.

Unfortunately, the technique cannot be applied to most blinding diseases because the needle often causes retinal detachment, making the situation worse. Yet, the standard AAV used in eye and other types of gene therapy cannot penetrate into tissue to reach the photoreceptors and other cells, such as retinal pigment epithelium, that need to be fixed. The retina is about 100,000 times thicker than the diameter of AAV, which is about 20 nanometers.

Years ago, Schaffer set out to find a way to “evolve” AAV to penetrate tissues, including eye and liver, as a way to deliver genes to specific cells. To date, he has generated 100 million variants of AAV — each carrying slightly different proteins on its coat — from which he and his colleagues selected five that were effective in penetrating the retina. They then used the best of these (7m8) to transport genes to cure two types of hereditary blindness for which there are mouse models: X-linked retinoschisis, which strikes only boys and makes their retinas look like Swiss cheese; and Leber’s congenital amaurosis. In each case, when injected into the vitreous humor, the AAV delivered the corrective gene to all areas of the retina and restored retinal cells nearly to normal.

When injected into the eye of a normal monkey, the viruses penetrated cells spottily across the retina, but almost completely in the very important fine-vision area called the fovea. Current viruses do not penetrate foveal cells at all.

Schaffer predicts that the viruses can be used not only to insert genes that restore function to non-working genes, but can knock out genes or halt processes that are actively killing retina cells, which may be the case in age-related macular degeneration.

“When I first got here 14 years ago, I really had the idea or the goal that I wanted to work on problems that would have direct impact on human health, and we are now getting there,” Schaffer said.

Coauthors include graduate students Deniz Dalkara and Leah C. Byrne of UC Berkeley’s Helen Wills Neuroscience Institute; graduate students Ryan R. Klimczak and Meike Visel of UC Berkeley’s Department of Molecular and Cell Biology; and Lu Yin and William H. Merigan of the Flaum Eye Institute and Center for Visual Science at the University of Rochester.

The work was supported by the Nanomedicine Development Center for the Optical Control of Biological Function of the National Institutes of Health and the Foundation Fighting Blindness.

Pleasure Response from Chocolate: You Can See It in the Eyes

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Posted on 2nd July 2013 by Pacific ClearVision Institute in General |Retina

The brain’s pleasure response to tasting food can be measured through the eyes using a common, low-cost ophthalmological tool, according to a study just published in the journal Obesity. If validated, this method could be useful for research and clinical applications in food addiction and obesity prevention.

Dr. Jennifer Nasser, an associate professor in the department of Nutrition Sciences in Drexel University’s College of Nursing and Health Professions, led the study testing the use of electroretinography (ERG) to indicate increases in the neurotransmitter dopamine in the retina.

Dopamine is associated with a variety of pleasure-related effects in the brain, including the expectation of reward. In the eye’s retina, dopamine is released when the optical nerve activates in response to light exposure.

Nasser and her colleagues found that electrical signals in the retina spiked high in response to a flash of light when a food stimulus (a small piece of chocolate brownie) was placed in participants’ mouths. The increase was as great as that seen when participants had received the stimulant drug methylphenidate to induce a strong dopamine response. These responses in the presence of food and drug stimuli were each significantly greater than the response to light when participants ingested a control substance, water.

“What makes this so exciting is that the eye’s dopamine system was considered separate from the rest of the brain’s dopamine system,” Nasser said. “So most people- and indeed many retinography experts told me this- would say that tasting a food that stimulates the brain’s dopamine system wouldn’t have an effect on the eye’s dopamine system.”

This study was a small-scale demonstration of the concept, with only nine participants. Most participants were overweight but none had eating disorders. All fasted for four hours before testing with the food stimulus.

If this technique is validated through additional and larger studies, Nasser said she and other researchers can use ERG for studies of food addiction and food science.

“My research takes a pharmacology approach to the brain’s response to food,” Nasser said. “Food is both a nutrient delivery system and a pleasure delivery system, and a ‘side effect’ is excess calories. I want to maximize the pleasure and nutritional value of food but minimize the side effects. We need more user-friendly tools to do that.”

The low cost and ease of performing electroretinography make it an appealing method, according to Nasser. The Medicare reimbursement cost for clinical use of ERG is about $150 per session, and each session generates 200 scans in just two minutes. Procedures to measure dopamine responses directly from the brain are more expensive and invasive. For example, PET scanning costs about $2,000 per session and takes more than an hour to generate a scan.