Study shows that people who undergo cataract surgery to correct visual impairment live longer

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in Cataracts |General

Australian researchers find a 40 percent lower mortality risk among patients who had their vision corrected through the procedure

People with cataract-related vision loss who have had cataract surgery to improve their sight are living longer than those with visual impairment who chose not to have the procedure, according to an Australian cohort study published this month in Ophthalmology, the journal of the American Academy of Ophthalmology. After comparing the two groups, the researchers found a 40 percent lower long-term mortality risk in those who had the surgery.

The research is drawn from data gathered in the Blue Mountains Eye Study, a population-based cohort study of vision and common eye diseases in an older Australian population. A total of 354 persons aged 49 years and older and diagnosed with cataract-related vision impairment – some of whom had undergone surgery and others who had not – were assessed between 1992 and 2007. Adjustments were made for age and gender as well as a number of mortality risk factors, including hypertension, diabetes, smoking, cardiovascular disease, body mass index and measures of frailty and comorbid disease. Follow-up visits took place after five and ten years since the baseline exam.

Previous research had indicated that older persons with visual impairment were likely to have greater mortality risk than their age peers with normal vision, and that cataract surgery might reduce this risk. These studies – unlike the Blue Mountains Eye Study – compared people who had undergone cataract surgery with those in the general population or with those who had not had cataract surgery, and did not link vision status to the surgical status.

“Our finding complements the previously documented associations between visual impairment and increased mortality among older persons,” said Jie Jin Wang, Ph.D., of the Westmead Millennium Institute and one of lead researchers of the study. “It suggests to ophthalmologists that correcting cataract patients’ visual impairment in their daily practice results in improved outcomes beyond that of the eye and vision, and has important impacts on general health.”

The association between correction of cataract-related visual impairment and reduced mortality risk is not clearly understood, but plausible factors may include improvements in physical and emotional well-being, optimism, greater confidence associated with independent living after vision improvement, as well as greater ability to comply with prescription medications.

Dr. Wang noted one limitation of the study is that participants with cataract-related visual impairment who did not have cataract surgery could have had other health problems that prevented them from undergoing surgery, and that these other health problems could partly explain the poorer survival among non-surgical participants. This issue is addressed by the researchers in a subsequent study.

Caused by the clouding of the lens, cataract is a leading cause of treatable visual impairment that will affect more than half of all Americans by the time they are 80 years old. Surgical removal of the opaque lens with an artificial lens implanted is a successful procedure of cataract treatment. If completing everyday tasks is difficult, cataract surgery should be discussed with an ophthalmologist – a medical doctor specializing in the diagnosis, medical and surgical treatment of eye diseases and conditions.

Human Eye Movements for Vision Are Remarkably Adaptable

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

When something gets in the way of our ability to see, we quickly pick up a new way to look, in much the same way that we would learn to ride a bike, according to a new study published in the Cell Press journal Current Biology on August 15.

Our eyes are constantly on the move, darting this way and that four to five times per second. Now researchers have found that the precise manner of those eye movements can change within a matter of hours. This discovery by researchers from the University of Southern California might suggest a way to help those with macular degeneration better cope with vision loss.

“The system that controls how the eyes move is far more malleable than the literature has suggested,” says Bosco Tjan of the University of Southern California. “We showed that people with normal vision can quickly adjust to a temporary occlusion of their foveal vision by adapting a consistent point in their peripheral vision as their new point of gaze.”

The fovea refers to the small, center-most portion of the retina, which is responsible for our high-resolution vision. We move our eyes to direct the fovea to different parts of a scene, constructing a picture of the world around us. In those with age-related macular degeneration, progressive loss of foveal vision leads to visual impairment and blindness.

In the new study, MiYoung Kwon, Anirvan Nandy, and Tjan simulated a loss of foveal vision in six normally sighted young adults by blocking part of a visual scene with a gray disc that followed the individuals’ eye gaze. Those individuals were then asked to complete demanding object-following and visual-search tasks. Within three hours of working on those tasks, people showed a remarkably fast and spontaneous adjustment of eye movements. Once developed, that change in their “point of gaze” was retained over a period of weeks and was reengaged whenever their foveal vision was blocked.

Tjan and his team say they were surprised by the rate of this adjustment. They note that patients with macular degeneration frequently do adapt their point of gaze, but in a process that takes months, not days or hours. They suggest that practice with a visible gray disc like the one used in the study might help speed that process of visual rehabilitation along. The discovery also reveals that the oculomotor (eye movement) system prefers control simplicity over optimality.

“Gaze control by the oculomotor system, although highly automatic, is malleable in the same sense that motor control of the limbs is malleable,” Tjan says. “This finding is potentially very good news for people who lose their foveal vision due to macular diseases. It may be possible to create the right conditions for the oculomotor system to quickly adjust,” Kwon adds.

iPhones for the Eyes: Smart Phone Photography to Help Diagnose Eye Disease

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

Retinal (or fundus) photography is an essential part of any ophthalmology practice. Commercial fundus cameras can cost tens to hundreds of thousands of dollars, making the technology out of reach for smaller ophthalmic practices and to physicians in third-world countries. In a recent study now on line, Massachusetts Eye and Ear researchers describe the relatively simple technique of fundus photography in human and rabbit eyes using a smartphone, an inexpensive app for the smartphone, and instruments that are readily available in an ophthalmic practice.

Smartphones are now being used more routinely in ophthalmology to document patients’ ocular conditions, the authors write. Previously described techniques of fundus imaging often proved difficult to repeat, partly because video capture using Apple’s built-in camera app in the iPhones cannot independently control the focus and the exposure during filming, which results in glare and poor image quality.

“Our technique provides a simpler and higher quality method to more consistently produce excellent images of a patient’s fundus,” said senior author Shizuo Mukai, M.D., Mass. Eye and Ear retina specialist and Harvard Medical School associate professor of Ophthalmology. “This technique has been extremely helpful for us in the emergency department setting, in-patient consultations, and during examinations under anesthesia as it provides a cheaper and portable option for high-quality fundus-image acquisition for documentation and consultation. This technique is well tolerated in awake patients most likely since the light intensity used is often well below that which is used in standard indirect ophthalmoscopy.”

Using the described technique of smartphone fundus photography with the use of iPhone 4 or iPhone 5, the app Filmic pro, and a 20D lens with or without a Koeppe lens, researchers were was able to capture excellent, high-quality fundus images in both children under anesthesia and in awake adults.

The best results were achieved in the operating room when a Koeppe lens was used in addition to the 20D lens; however, excellent images were acquired with the 20D lens alone in the clinic and emergency room setting as well as in the operating room. Researchers report that even first-year ophthalmology residents were able to master this technique in a relatively short period.

“This technique is relatively inexpensive and simple to master, and takes advantage of the expanding mobile-telephone networks for telemedicine,” Dr. Mukai said. “We expect that the quality of the images achieved using this technique will continue to improve as higher-resolution cameras with larger sensors and better image stabilization is incorporated into newer smartphones.”

New Laser Provides Cutting-Edge Treatment for Diabetes, Retinal Diseases

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

A new laser is helping experts at the Truhlsen Eye Institute at the University of Nebraska Medical Center provide better treatment for eye diseases. This advanced laser can prevent blindness for some patients with serious conditions.

“This new laser with yellow light is currently the only one of its caliber in the U.S., and there’s only one other being used in the world right now,” said Quan Dong Nguyen, M.D., the McGaw Memorial Endowed Chair in Ophthalmology and director of the Eye Institute.

On July 22, the first patient received treatment from the laser for proliferative diabetic retinopathy, the most severe stage of eye disease caused by diabetes.

“This laser is the most cutting-edge laser device available today,” said Diana Do, M.D., associate professor of ophthalmology and director of the Carl Camras Center for Innovative Clinical Research at the Truhlsen Eye Institute and the retina specialist who performed the first treatment.

“It allows us to apply a large number of laser spots in a variety of patterns,” Dr. Do said. “Overall, it is more effective, efficient and may be safer than traditional lasers.”

Traditional lasers are limited in the number of patterns and pulsing they can accommodate, whereas the new laser allows for more nuanced and problem-specific targeting, Dr. Do said.

The laser provides treatment for various rare eye diseases, including retinal vein occlusion, neovascular glaucoma, and retinal tears. In addition, with micropulse application capability, it also can be combined with other therapies to treat diabetic macular edema, the most common cause of moderate vision loss for diabetes patients.

“With diabetes rates on the rise nationally and in Nebraska, more and more patients will be able to benefit from the superior treatment that new technology like this can bring,” Dr. Do said.

The full name of the laser is the Supra Scan Multi-spot Laser. It is manufactured by Quantel Medical, which is headquartered in Paris, France.

The Truhlsen Eye Institute, which opened in two months ago at 3902 Leavenworth St., is the newest building on UNMC’s campus and offers state-of-the-art eye care in many eye subspecialties as well as routine prescription and optical shop services.

To make an appointment at the Truhlsen Eye Institute, please call 402-559-2020.

Through world-class research and patient care, UNMC generates breakthroughs that make life better for people throughout Nebraska and beyond. Its education programs train more health professionals than any other institution in the state.

Gene Regulator Is Key to Healthy Retinal Development and Good Vision in Adulthood

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

Scientists are developing a clearer picture of how visual systems develop in mammals. The findings offer important clues to the origin of retinal disorders later in life.

In research published this week in the Journal of Neuroscience, University at Buffalo scientists and colleagues focused on a particular protein, called a transcription factor, that regulates gene activity necessary for the development of one type of retinal neuron, the horizontal cells.

Horizontal cells process visual information by integrating and regulating input from rod and cone photoreceptors, which allow eyes to adjust to see well in both bright and dim light conditions.

“We have found that activation of the transcription factor named Onecut1 is essential for the formation of horizontal cells,” explains Xiuqian Mu, PhD, assistant professor in the departments of Ophthalmology and Biochemistry in the UB School of Medicine and Biomedical Sciences.

The researchers came to this conclusion after creating mice that lacked Onecut1. In these knockout mice, the number of horizontal cells was 80 percent lower than in normal mice. The researchers were surprised to find that the removal of Onecut1 also had an impact on photoreceptor cells, the rods and cones that absorb light in the retina and convert that energy to an electrical impulse eventually conveyed to the brain.

During development, Mu explains, the removal of Onecut1 only appeared to impact the horizontal cells. However, by the time these mice reached adulthood, around 8 months old, the level of photoreceptor cells in these knockout mice was less than half the normal level.

“Because degradation of photoreceptors is believed to be a major factor in retinal diseases, such as retinitis pigmentosa and Leber’s congenital amaurosis, this finding, that horizontal cells are necessary for the normal survival of photoreceptor cells, is novel and significant,” says Mu. “Many retinal diseases are manifested by the degeneration of photoreceptor cells.”

This finding was unexpected, Mu explains, because most investigations into the degeneration of photoreceptor cells have involved genes that directly affect photoreceptor cell development.

“People haven’t been looking at horizontal cells,” he says. “We didn’t think that they’d be involved in photoreceptor cell degradation.

“With this finding, we have discovered that retinal horizontal cells are required for maintaining the integrity of the retina and that their deficiency can lead to retinal degradation,” explains Mu.

He notes that in most cases where photoreceptor cells die, it’s because they are somehow defective.

“But in this case, the photoreceptor cells are fine in the beginning, so the death of the photoreceptor cells is a secondary affair that is somehow driven by the deficiency in horizontal cells,” he says.

UB co-author Steven J. Fliesler, PhD, Meyer H. Riwchun Endowed Chair Professor, vice-chair and director of research in the Department of Ophthalmology and professor in the Department of Biochemistry, notes that this finding could open up a new area of study.

“One scenario we have speculated upon is that there are important supportive interactions between horizontal cells and photoreceptors that are required to maintain photoreceptor function and viability,” Fliesler says. “When horizontal cells are blocked from being formed — the immediate consequence of knocking out Onecut1 — the photoreceptors don’t get what they need to survive, so they degenerate and die later on.”

The majority of the research was conducted in the UB Department of Ophthalmology/Ross Eye Institute and the developmental genomics group at UB’s New York State Center of Excellence in Bioinformatics and Life Sciences.

First author on the paper is Fuguo Wu of UB. Other UB co-authors are Renzhong Li, Tadeusz J. Kaczynski, Darshan Sapkota. Additional co-authors are Yumiko Umino and Eduardo Solessio of SUNY Upstate Medical University, Shengguo Li and Mengqing Xiang of the University of Medicine and Dentistry of New Jersey, David M. Sherry of the University of Oklahoma Health Sciences Center and Maureen Gannon of Vanderbilt University Medical Center.

Mu, Fliesler and Solessio also are faculty members of the SUNY Eye Institute, a SUNY-wide eye research consortium.

The work was supported by the Whitehall Foundation, the National Eye Institute, the SUNY/RF Research Collaboration Fund, Research to Prevent Blindness, the Oklahoma Center for the Advancement of Science and Technology, the Lions of Central New York, and resources and facilities provided by the Veterans Administration Western NY Healthcare System.

Therapeutic Eye Injections May Be Needed Less Often

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

Johns Hopkins biomedical engineers have teamed up with clinicians to create a new drug-delivery strategy for a type of central vision loss caused by blood vessel growth at the back of the eye, where such growth should not occur. In addition to testing a new drug that effectively stops such runaway vessel growth in mice, the team gave the drug a biodegradable coating to keep it in the eye longer. If proven effective in humans, the engineers say, it could mean only two or three needle sticks to the eye per year instead of the monthly injections that are the current standard of care.

The new drug, in its time-release coating, was tested in mice with abnormalities similar to those experienced by people with neovascular age-related macular degeneration, or “wet” AMD. A description of the study results, currently available online, will be published in the October issue of the journal Biomaterials.

“If you lose central vision, you can’t drive a car and you can’t see your grandchildren,” says Jordan Green, Ph.D., assistant professor of biomedical engineering and ophthalmology at The Johns Hopkins University. “You’re willing to do what it takes to keep your sight. We hope that our system will work in people, and make invasive treatments much less frequent, and therefore easier to comply with, and safer.”

According to Peter Campochiaro, M.D., the George S. & Dolores Doré Eccles Professor of Ophthalmology & Neuroscience, approximately 200,000 Americans suffer from central vision loss caused by wet AMD. The macula is a few square centimeters of tissue in the center of the retina at the back of the eye. It is responsible for the majority of a person’s high-resolution vision, especially the high-res vision needed for driving and reading. There are normally no blood vessels in the outer part of the retina because it needs to be unobstructed to capture complete images. In patients with wet AMD, blood vessels from behind the retina can break through into the macula and leak fluid that reduces vision. This initially causes reversible loss of vision, but, if left untreated, visual loss becomes permanent.

Currently, wet AMD patients are treated with frequent (as often as once a month) injections into the eye of a drug that blocks one of the major stimulators of abnormal blood vessel growth. “Patients are given localized antibacterial and pain-numbing agents, and then a very fine needle is passed through the white of the eye into the central cavity where the drug is injected. It’s not painful, but it isn’t something that patients enjoy,” says Campochiaro. “The frequent visits for injections are a burden and each injection carries a small risk of infection, so one of our goals is to find new approaches that allow for fewer visits and injections.”

Green’s laboratory, which specializes in designing new drug-delivery systems, worked with Campochiaro and Aleksander Popel, Ph.D., professor of biomedical engineering, whose laboratory discovered the new drug — a short piece of protein that blocks the growth of unwanted blood vessels. (The drugs currently on the market for treating wet AMD are longer protein pieces or full-length proteins that could become inactive if given a biodegradable coating.)

When the team tested the drug on cells grown in the lab, they found that it killed blood vessel cells and prevented growth of new blood vessels. The same effect was found when the drug was injected into the eyes of mice with abnormal blood vessels like those seen in wet AMD, but, as with the current standard treatment, the drug was only effective for about four weeks since the watery contents inside the eye gradually flushed it out.

The team’s solution, says Green, was to slow the release and depletion of the drug by covering it in non-toxic, biodegradable coatings. They first created “nanoparticles,” tiny little spheres filled with the drug. When the spheres were placed in a watery environment, the water gradually broke down the coating and released the drug a little at a time. To maximize this effect, the team created larger spheres, called microparticles, filled with about a hundred nanoparticles per microparticle, and held together by another type of biodegradable “glue.” The end result is something like a scoop of gumball ice cream. As the ice cream gets licked away, more and more gumballs (nanoparticles) are exposed.

Testing their microparticles in mice, the team found that the drug persisted in their eyes for at least 14 weeks, more than three times as long as the current treatment. Green says that the treatments may last longer in humans than in mice, but clinical trials will not begin before further testing in other animals.

The Eyes Have It: How Organic Mercury Can Interfere With Vision

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

More than one billion people worldwide rely on fish as an important source of animal protein, states the United Nations Food and Agriculture Organization. And while fish provide slightly over 7 per cent of animal protein in North America, in Asia they represent about 23 per cent of consumption.

Humans consume low levels of methylmercury by eating fish and seafood. Methylmercury compounds specifically target the central nervous system, and among the many effects of their exposure are visual disturbances, which were previously thought to be solely due to methylmercury-induced damage to the brain visual cortex. However, after combining powerful synchrotron X-rays and methylmercury-poisoned zebrafish larvae, scientists have found that methylmercury may also directly affect vision by accumulating in the retinal photoreceptors, i.e. the cells that respond to light in our eyes.

Dr. Gosia Korbas, BioXAS staff scientist at the Canadian Light Source (CLS), says the results of this experiment show quite clearly that methylmercury localizes in the part of the photoreceptor cell called the outer segment, where the visual pigments that absorb light reside.

“There are many reports of people affected by methylmercury claiming a constricted field of vision or abnormal colour vision,” said Korbas. “Now we know that one of the reasons for their symptoms may be that methylmercury directly targets photoreceptors in the retina.”

Korbas and the team of researchers from the University of Saskatchewan including Profs. Graham George, Patrick Krone and Ingrid Pickering conducted their experiments using three X-ray fluorescence imaging beamlines (2-ID-D, 2-ID-E and 20-ID-B) at the Advanced Photon Source, Argonne National Laboratory near Chicago, US, as well as the scanning X-ray transmission beamline (STXM) at the Canadian Light Source in Saskatoon, Canada.

After exposing zebrafish larvae to methylmercury chloride in water, the team was able to obtain high-resolution maps of elemental distributions, and pinpoint the localization of mercury in the outer segments of photoreceptor cells in both the retina and pineal gland of zebrafish specimens. The results of the research were published in ACS Chemical Biology under the title “Methylmercury Targets Photoreceptor Outer Segments.”

Korbas said zebrafish are an excellent model for investigating the mechanisms of heavy metal toxicity in developing vertebrates. One of the reasons for that is their high degree of correlation with mammals. Recent studies have demonstrated that about 70 per cent of protein-coding human genes have their counterparts in zebrafish, and 84 per cent of genes linked to human diseases can be found in zebrafish.

“Researchers are studying the potential effects of low level chronic exposure to methylmercury, which is of global concern due to methylmercury presence in fish, but the message that I want to get across is that such exposures may negatively affect vision. Our study clearly shows that we need more research into the direct effects of methylmercury on the eye,” Korbas concluded.

Making Connections in the Eye: Wiring Diagram of Retinal Neurons Is First Step Toward Mapping the Human Brain

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

The human brain has 100 billion neurons, connected to each other in networks that allow us to interpret the world around us, plan for the future, and control our actions and movements. MIT neuroscientist Sebastian Seung wants to map those networks, creating a wiring diagram of the brain that could help scientists learn how we each become our unique selves.

In a paper appearing in the Aug. 7 online edition of Nature, Seung and collaborators at MIT and the Max Planck Institute for Medical Research in Germany have reported their first step toward this goal: Using a combination of human and artificial intelligence, they have mapped all the wiring among 950 neurons within a tiny patch of the mouse retina.

Composed of neurons that process visual information, the retina is technically part of the brain and is a more approachable starting point, Seung says. By mapping all of the neurons in this 117-micrometer-by-80-micrometer patch of tissue, the researchers were able to classify most of the neurons they found, based on their patterns of wiring. They also identified a new type of retinal cell that had not been seen before.

“It’s the complete reconstruction of all the neurons inside this patch. No one’s ever done that before in the mammalian nervous system,” says Seung, a professor of computational neuroscience at MIT.

Other MIT authors of the paper are former postdoc Srinivas Turaga and former graduate student Viren Jain. The Max Planck team was led by Winfried Denk, a physicist and the Max Planck Institute’s director. Moritz Helmstaedter, a research group leader at the Max Planck Institute, is the lead author of the paper, and Kevin Briggman, a former postdoc at Max Planck, is also an author.

Tracing connections

Neurons in the retina are classified into five classes: photoreceptors, horizontal cells, bipolar cells, amacrine cells and ganglion cells. Within each class are many types, classified by shape and by the connections they make with other neurons.

“Neurons come in many types, and the retina is estimated to contain 50 to 100 types, but they’ve never been exhaustively characterized. And their connections are even less well known,” Seung says.

In this study, the research team focused on a section of the retina known as the inner plexiform layer, which is one of several layers sandwiched between the photoreceptors, which receive visual input, and the ganglion cells, which relay visual information to the brain via the optic nerve. The neurons of the inner plexiform layer help to process visual information as it passes from the surface of the eye to the optic nerve.

To map all of the connections in this small patch of retina, the researchers first took electron micrographs of the targeted section. The Max Planck researchers obtained these images using a technique called serial block face scanning electron microscopy, which they invented to generate high-resolution three-dimensional images of biological samples.

Developing a wiring diagram from these images required both human and artificial intelligence. First, the researchers hired about 225 German undergraduates to trace the “skeleton” of each neuron, which took more than 20,000 hours of work (a little more than two years).

To flesh out the bodies of the neurons, the researchers fed these traced skeletons into a computer algorithm developed in Seung’s lab, which expands the skeletons into full neuron shapes. The researchers used machine learning to train the algorithm, known as a convolutional network, to detect the boundaries between neurons. Using those as reference points, the algorithm can fill in the entire body of each neuron.

“Tracing neurons in these images is probably one of the world’s most challenging computer vision problems. Our convolutional networks are actually deep artificial neural networks designed with inspiration from how our own visual system processes visual information to solve these difficult problems,” Turaga says.

If human workers were to fill in the entire neuron body, it would take 10 to 100 times longer than just drawing the skeleton. “This speeds up the whole process,” Seung says. “It’s a way of combining human and machine intelligence.”

The only previous complete wiring diagram, which mapped all of the connections between the 302 neurons found in the worm Caenorhabditis elegans, was reported in 1986 and required more than a dozen years of tedious labor.

“I think this is going to be a really significant paper in the history of how we study complex systems,” says Richard Masland, a professor of ophthalmology at the Massachusetts Eye and Ear Infirmary, who was not part of the research team. “This paper identifies circuit motifs that are interesting but really are just symbolic of the many types of questions that could be answered using these techniques.”

Classifying neurons

Wiring diagrams allow scientists to see where neurons connect with each other to form synapses — the junctions that allow neurons to relay messages. By analyzing how neurons are connected to each other, researchers can classify different types of neurons.

The researchers were able to identify most of the 950 neurons included in the new retinal-wiring diagram based on their connections with other neurons, as well as the shape of the neuron. A handful of neurons could not be classified because there was only one of their type, or because only a fragment of the neuron was included in the imaged sample.

“We haven’t completed the project of classifying types but this shows that it should be possible. This method should be able to do it, in principle, if it’s scaled up to a larger piece of tissue,” Seung says.

In this study, the researchers identified a new class of bipolar cells, which relay information from photoreceptors to ganglion cells. However, further study is needed to determine this cell type’s exact function.

Seung’s lab is now working on a wiring diagram of a larger piece of the retina — 0.3 millimeter by 0.3 millimeter — using a slightly different approach. In that study, the researchers first feed their electron micrographs into the computer algorithm, then ask human volunteers to check over the computer’s work and correct mistakes through a crowd-sourcing project known as EyeWire.

The research was funded by the Max Planck Society, the Howard Hughes Medical Institute and the Gatsby Charitable Foundation.

Rare Gene Variant Linked to Macular Degeneration

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

An international team of researchers, led by scientists at The Genome Institute at Washington University School of Medicine in St. Louis and the University of Michigan School of Public Health in Ann Arbor, has identified a gene mutation linked to age-related macular degeneration (AMD), the leading cause of blindness in Americans over age 50.

It’s not the first gene variation linked to AMD, but it is the first to suggest a mechanism where the variant may contribute to the disease. The researchers report that a change in the C3 gene, which plays a role in inflammation and in the body’s immune response, also contributes to macular degeneration.

The study was published online Sept. 15 in the journal Nature Genetics.

“In past studies of AMD, there is a clear relationship between the complement pathway and the onset of this disease,” said co-senior investigator Elaine R. Mardis, PhD. “The complement system is part of the immune system that helps amplify or ‘complement’ the efforts of immune cells to fight infections. So the idea is that the gene variant interferes with the complement pathway’s normal function throughout life, and that can damage the retina over time, which ultimately leads to AMD’s emergence.”

The researchers sequenced DNA from 10 regions of the genome that had been linked to AMD in previous genetic studies. They analyzed a total of 57 genes in 2,335 patients with macular degeneration. Then the researchers sequenced the same genes in 789 people of the same age who did not have AMD.

The search turned up two gene variants: one in the C3 complement gene, and an alteration that had been identified in previous studies of macular degeneration.

“Finding the variant that had been identified previously helped confirm that we were on the right track,” explained Mardis, a professor of genetics and co-director of the Genome Institute. “And it’s likely this new variant was discovered because of the very large number of patients whose DNA we sequenced. By analyzing so many AMD patients, it was possible to find variants that may not have been identified in a smaller patient sample and to establish that this C3 gene variant is unique to people with AMD.”

The two gene variants together contribute to a three-fold increased risk for macular degeneration. Mardis and her co-investigators hypothesize that the mutations work in tandem to increase AMD risk by interfering with the inactivation of complement in the retina.

“When you have these mutations, interactions between the proteins that cascade in the complement pathway are altered,” Mardis said. “And when they’re altered, the secondary response to infection, which involves complement, also is altered. So our hypothesis is that over time, because of the role of the complement pathway in the retina, damage begins to accrue, and eventually that leads to vision loss.”

The next step, according to Mardis, is to look at additional DNA regions in the more than 2,000 patients and controls who were involved in this study. The researchers will broaden their look across the genome and go beyond the 10 regions of DNA that were analyzed in this study.

“We hope to identify new genes — perhaps more genes in the complement pathway, perhaps genes in other inflammatory response pathways, or in areas we wouldn’t have anticipated finding any genes related to AMD,” she said. “We’re taking a wide look at the genome to see what turns up.”

Beating Blindness With Vegetable Oil

0 comments

Posted on 30th September 2013 by Pacific ClearVision Institute in General |Retina

Scientists working at the Research Center on Aging at the Health and Social Services Centre — University Institute of Geriatrics of Sherbrooke (CSSS-IUGS) have been studying strategies for protecting retinal pigment epithelium (RPE) cells. Dysfunction of the RPE is found in retinopathy and age-related macular degeneration, which is the leading cause of blindness of elderly people in developed countries.

Findings published today in the Canadian Journal of Physiology and Pharmacology suggest that incubating retinal cells with vegetable oils induces biochemical and biophysical changes in the cell membrane, which may have a beneficial effect in preventing or slowing the development of retinopathy.

“Membrane fluidity, which refers to the viscosity of the lipid bi-layer of a cell membrane, is a marker of the cell function,” explained Prof. A. Khalil, professor at the Université de Sherbrooke and principal investigator of the study. “A decrease of membrane fluidity can affect the rotation and diffusion of proteins and other bio-molecules within the membrane, thereby affecting the functions of these molecules. Whereas, an increase in membrane fluidity makes for a more flexible membrane and facilitates the transmission of light through the eye.”

The researchers discovered that vegetable oil fatty acids incorporate in retina cells and increase the plasma membrane fluidity. They concluded that a diet low in trans-unsaturated fats and rich in omega-3 fatty acids and olive oil may reduce the risk of retinopathy. In addition, the research suggests that replacing the neutral oil used in eye drops with oil that possesses valuable biological properties for the eye could also contribute to the prevention of retina diseases.