Posts tagged photoreceptors
Articles and news from the latest research reports.
Discovery of a new mechanism that can lead to blindness
An important scientific breakthrough by a team of IRCM researchers led by Michel Cayouette, PhD, is being published today by The Journal of Neuroscience. The Montréal scientists discovered that a protein found in the retina plays an essential role in the function and survival of light-sensing cells that are required for vision. These findings could have a significant impact on our understanding of retinal degenerative diseases that cause blindness.
The researchers studied a process called compartmentalization, which establishes and maintains different compartments within a cell, each containing a specific set of proteins. This process is crucial for neurons (nerve cells) to function properly.
“Compartments within a cell are much like different parts of a car,” explains Vasanth Ramamurthy, PhD, first author of the study. “In the same way that gas must be in the fuel tank in order to power the car’s engine, proteins need to be in a specific compartment to properly exercise their functions.”
A good example of compartmentalization is observed in a specialized type of light-sensing neurons found in the retina, the photoreceptors, which are made up of different compartments containing specific proteins essential for vision.
“We wanted to understand how compartmentalization is achieved within photoreceptor cells,” says Dr. Cayouette, Director of the Cellular Neurobiology research unit at the IRCM. “Our work identified a new mechanism that explains this process. More specifically, we found that a protein called Numb functions like a traffic controller to direct proteins to the appropriate compartments.”
“We demonstrated that in the absence of Numb, photoreceptors are unable to send a molecule essential for vision to the correct compartment, which causes the cells to progressively degenerate and ultimately die,” adds Dr. Ramamurthy, who carried out the project in Dr. Cayouette’s laboratory in collaboration with Christine Jolicoeur, research assistant. “This is important because the death of photoreceptor cells is known to cause retinal degenerative diseases in humans that lead to blindness. Our work therefore provides a new piece of the puzzle to help us better understand how and why the cells die.”
“We believe our results could eventually have a substantial impact on the development of treatments for retinal degenerative diseases, like retinitis pigmentosa and Leber’s congenital amaurosis, by providing novel drug targets to prevent photoreceptor degeneration,” concludes Dr. Cayouette.
According to the Foundation Fighting Blindness Canada, millions of people in North America live with varying degrees of irreversible vision loss because they have an untreatable, degenerative eye disorder that affects the retina. Research aiming to better understand what causes vision loss could lead to preserving and restoring sight.
(Source: ircm.qc.ca)
Researchers Use Human Stem Cells to Create Light-Sensitive Retina in a Dish
Using a type of human stem cell, Johns Hopkins researchers say they have created a three-dimensional complement of human retinal tissue in the laboratory, which notably includes functioning photoreceptor cells capable of responding to light, the first step in the process of converting it into visual images.
(Image caption: Rod photoreceptors (in green) within a “mini retina” derived from human iPS cells in the lab. Image courtesy of Johns Hopkins Medicine)
“We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light,” says study leader M. Valeria Canto-Soler, Ph.D., an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine. She says the work, reported online June 10 in the journal Nature Communications, “advances opportunities for vision-saving research and may ultimately lead to technologies that restore vision in people with retinal diseases.”
Like many processes in the body, vision depends on many different types of cells working in concert, in this case to turn light into something that can be recognized by the brain as an image. Canto-Soler cautions that photoreceptors are only part of the story in the complex eye-brain process of vision, and her lab hasn’t yet recreated all of the functions of the human eye and its links to the visual cortex of the brain. “Is our lab retina capable of producing a visual signal that the brain can interpret into an image? Probably not, but this is a good start,” she says.
The achievement emerged from experiments with human induced pluripotent stem cells (iPS) and could, eventually, enable genetically engineered retinal cell transplants that halt or even reverse a patient’s march toward blindness, the researchers say.
The iPS cells are adult cells that have been genetically reprogrammed to their most primitive state. Under the right circumstances, they can develop into most or all of the 200 cell types in the human body. In this case, the Johns Hopkins team turned them into retinal progenitor cells destined to form light-sensitive retinal tissue that lines the back of the eye.
Using a simple, straightforward technique they developed to foster the growth of the retinal progenitors, Canto-Soler and her team saw retinal cells and then tissue grow in their petri dishes, says Xiufeng Zhong, Ph.D., a postdoctoral researcher in Canto-Soler’s lab. The growth, she says, corresponded in timing and duration to retinal development in a human fetus in the womb. Moreover, the photoreceptors were mature enough to develop outer segments, a structure essential for photoreceptors to function.
Retinal tissue is complex, comprising seven major cell types, including six kinds of neurons, which are all organized into specific cell layers that absorb and process light, “see,” and transmit those visual signals to the brain for interpretation. The lab-grown retinas recreate the three-dimensional architecture of the human retina. “We knew that a 3-D cellular structure was necessary if we wanted to reproduce functional characteristics of the retina,” says Canto-Soler, “but when we began this work, we didn’t think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do.”
When the retinal tissue was at a stage equivalent to 28 weeks of development in the womb, with fairly mature photoreceptors, the researchers tested these mini-retinas to see if the photoreceptors could in fact sense and transform light into visual signals.
They did so by placing an electrode into a single photoreceptor cell and then giving a pulse of light to the cell, which reacted in a biochemical pattern similar to the behavior of photoreceptors in people exposed to light.
Specifically, she says, the lab-grown photoreceptors responded to light the way retinal rods do. Human retinas contain two major photoreceptor cell types called rods and cones. The vast majority of photoreceptors in humans are rods, which enable vision in low light. The retinas grown by the Johns Hopkins team were also dominated by rods.
Canto-Soler says that the newly developed system gives them the ability to generate hundreds of mini-retinas at a time directly from a person affected by a particular retinal disease such as retinitis pigmentosa. This provides a unique biological system to study the cause of retinal diseases directly in human tissue, instead of relying on animal models.
The system, she says, also opens an array of possibilities for personalized medicine such as testing drugs to treat these diseases in a patient-specific way. In the long term, the potential is also there to replace diseased or dead retinal tissue with lab-grown material to restore vision.
(Source: hopkinsmedicine.org)
Biologists Identify New Neural Pathway in Eyes that Aids in Vision
A type of retina cell plays a more critical role in vision than previously known, a team led by Johns Hopkins University researchers has discovered.
Working with mice, the scientists found that the ipRGCs – an atypical type of photoreceptor in the retina – help detect contrast between light and dark, a crucial element in the formation of visual images. The key to the discovery is the fact that the cells express melanopsin, a type of photopigment that undergoes a chemical change when it absorbs light.
“We are quite excited that melanopsin signaling contributes to vision even in the presence of functional rods and cones,” postdoctoral fellow Tiffany M. Schmidt said.
Schmidt is lead author of a recently published study in the journal Neuron. The senior author is Samer Hattar, associate professor of biology in the university’s Krieger School of Arts and Sciences. Their findings have implications for future studies of blindness or impaired vision.
Rods and cones are the most well-known photoreceptors in the retina, activating in different light environments. Rods, of which there are about 120 million in the human eye, are highly sensitive to light and turn on in dim or low-light environments. Meanwhile the 6 million to 7 million cones in the eye are less sensitive to light; they drive vision in brighter light conditions and are essential for color detection.
Rods and cones were thought to be the only light-sensing photoreceptors in the retina until about a decade ago when scientists discovered a third type of retinal photoreceptor – the ipRGC, or intrinsically photosensitive retinal ganglion cell – that contains melanopsin. Those cells were thought to be needed exclusively for detecting light for non-image-dependent functions, for example, to control synchronization of our internal biological clocks to daytime and the constriction of our pupils in response to light.
“Rods and cones were thought to mediate vision and ipRGCs were thought to mediate these simple light-detecting functions that happen outside of conscious perception,” Schmidt said. “But our experiments revealed that ipRGCs influence a greater diversity of behaviors than was previously known and actually contribute to an important aspect of image-forming vision, namely contrast detection.”
The Johns Hopkins team along with other scientists conducted several experiments with mice and found that when melanopin was present in the retinal ganglion cells, the mice were better able to see contrast in a Y-shaped maze, known as the visual water task test. In the test, mice are trained to associate a pattern with a hidden platform that allows them to escape the water. Mice that had the melanopsin gene intact had higher contrast sensitivity than mice that lack the gene.
“Melanopsin signaling is essential for full contrast sensitivity in mouse visual functions,” said Hattar. “The ipRGCs and melanopsin determine the threshold for detecting edges in the visual scene, which means that visual functions that were thought to be solely mediated by rods and cones are now influenced by this system. The next step is to determine if melanopsin plays a similar role in the human retina for image-forming visual functions.”
(Source: releases.jhu.edu)
For resetting circadian rhythms, neural cooperation is key
Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th have found that the clusters of brain cells responsible for each of those activity peaks—known as the morning and evening oscillators, respectively—don’t work alone. For flies’ internal clocks to follow the sun, cooperation is key.
"Without proper synchronization, circadian clocks are useless or can even be deleterious to organisms," said Patrick Emery from the University of Massachusetts Medical School. "In addition, most organisms have to detect changes in day length to adapt their rhythms to seasons.
"Our work clearly shows that light is detected by individual neurons that then communicate with each other to properly define the phase of circadian behavior," he added. "This emphasizes the importance of neural interaction in the generation of properly phased circadian rhythms."
In the brains of Drosophila fruit flies, there are approximately 150 circadian neurons, explained Emery and coauthor Yong Zhang, including a small group of morning oscillators that promote activity early in the day and another group of evening oscillators that promote activity later. Morning oscillators also set the pace of molecular rhythms in other parts of the brain, and hence the phase of circadian behavior. Scientists had thought they did this by relying heavily on their own sensitivity to light—what Emery calls “cell-autonomous photoreception.” Indeed, these cells do express fruit flies’ dedicated photoreceptor Cryptochrome (CRY). But recent evidence suggested that something was missing from that simple view.
In the new study, the researchers manipulated CRY’s ability to function through another clock component, known as JET (short for Jetlag), in different circadian neurons and watched what happened. The studies show that light detection by the morning oscillators isn’t enough to keep flies going about their business in a timely way. They need those evening oscillators too.
JET’s role is bigger than expected as well. In addition to enabling cell-autonomous light sensing, the protein also allows distinct circadian neurons to talk to each other in rapid fashion after light exposure, although the researchers don’t yet know how.
The new model also suggests that flies and mammals have more similarities than had been appreciated when it comes to synchronizing their activities to the sun, the researchers say. In mammals, specific neurons of the circadian pacemaker of the brain (known as the Suprachiasmatic Nucleus or SCN) receive light input from the retina. Those cells then communicate with pacemaker neurons, which resets the circadian network as a whole.
Computer models help decode cells that sense light without seeing
Researchers have found that the melanopsin pigment in the eye is potentially more sensitive to light than its more famous counterpart, rhodopsin, the pigment that allows for night vision.
For more than two years, the staff of the Laboratory for Computational Photochemistry and Photobiology (LCPP) at Ohio’s Bowling Green State University (BGSU), have been investigating melanopsin, a retina pigment capable of sensing light changes in the environment, informing the nervous system and synchronizing it with the day/night rhythm. Most of the study’s complex computations were carried out on powerful supercomputer clusters at the Ohio Supercomputer Center (OSC).
The research recently appeared in the Proceedings of the National Academy of Sciences USA, in an article edited by Arieh Warshel, Ph.D., of the University of Southern California. Warshel and two other chemists received the 2013 Nobel Prize in Chemistry for developing multiscale models for complex chemical systems, the same techniques that were used in conducting the BGSU study, “Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins.”
“The retina of vertebrate eyes, including those of humans, is the most powerful light detector that we know,” explains Massimo Olivucci, Ph.D., a research professor of Chemistry and director of LCPP in the Center for Photochemical Sciences at BGSU. “In the human eye, light coming through the lens is projected onto the retina where it forms an image on a mosaic of photoreceptor cells that transmits information from the surrounding environment to the brain’s visual cortex. In extremely poor illumination conditions, such as those of a star-studded night or ocean depths, the retina is able toperceive intensities corresponding to only a few photons, which are indivisible units of light. Such extreme sensitivity is due to specialized photoreceptor cells containing a light sensitive pigment called rhodopsin.”
For a long time, it was assumed that the human retina contained only photoreceptor cells specialized in dim-light and daylight vision, according to Olivucci. However, recent studies revealed the existence of a small number of intrinsically photosensitive nervous cells that regulate non-visual light responses. These cells contain a rhodopsin-like protein named melanopsin, which plays a role in the regulation of unconscious visual reflexes and in the synchronization of the body’s responses to the dawn/dusk cycle, known as circadian rhythms or the “body clock,” through a process known as photoentrainment.
The fact that the melanopsin density in the vertebrate retina is 10,000 times lower than that of rhodopsin density, and that, with respect to the visual photoreceptors, the melanopsin-containing cells capture a million-fold fewer photons, suggests that melanopsin may be more sensitive than rhodopsin. The comprehension of the mechanism that makes this extreme light sensitivity possible appears to be a prerequisite to the development of new technologies.
Both rhodopsin and melanopsin are proteins containing a derivative of vitamin A, which serves as an “antenna” for photon detection. When a photon is detected, the proteins are set in an activated state, through a photochemical transformation, which ultimately results in a signal being sent to the brain. Thus, at the molecular level, visual sensitivity is the result of a trade-off between two factors: light activation and thermal noise. It is currently thought that light-activation efficiency (i.e., the number of activation events relative to the total number of detected photons) may be related to its underlying speed of chemical transformation. On the other hand, the thermal noise depends on the number of activation events triggered by ambient body heat in the absence of photon detection.
“Understanding the mechanism that determines this seemingly amazing light sensitivity of melanopsin may open up new pathways in studying the evolution of light receptors in vertebrate and, in turn, the molecular basis of diseases, such as “seasonal affecting disorders,” Olivucci said. “Moreover, it provides a model for developing sub-nanoscale sensors approaching the sensitivity of a single-photon.”
For this reason, the LCPP group – working together with Francesca Fanelli, Ph.D., of Italy’s Università di Modena e Reggio Emilia – has used the methodology developed by Warshel and his colleagues to construct computer models of human melanopsin, bovine rhodopsin and squid rhodopsin. The models were constructed by BGSU research assistant Samer Gozem, Ph.D., BGSU visiting graduate student Silvia Rinaldi, who now has completed his doctorate, and visiting research assistant Federico Melaccio, Ph.D. – both visiting from Italy’s Università di Siena. The models were used to study the activation of the pigments and show that melanopsin light activation is the fastest, and its thermal activation is the slowest, which was expected for maximum light sensitivity.
The computer models of human melanopsin, and bovine and squid rhodopsins, provide further support for a theory reported by the LCPP group in the September 2012 issue of Science Magazine which explained the correlation between thermal noise and perceived color, a concept first proposed by the British neuroscientist Horace Barlow in 1957. Barlow suggested the existence of a link between the color of light perceived by the sensor and its thermal noise and established that the minimum possible thermal noise is achieved when the absorbing light has a wavelength around 470 nanometers, which corresponds to blue light.
“This wavelength and corresponding bluish color matches the wavelength that has been observed and simulated in the LCPP lab,” said Olivucci. “In fact, our calculations also indicate that a shift from blue to even shorter wavelengths (i.e. indigo and violet) will lead to an inversion of the trend and an increase of thermal noise towards the higher levels seen for a red color. Therefore, melanopsin may have been selected by biological evolution to stand exactly at the border between two opposite trends to maximize light sensitivity.”
Study with totally blind people shows how light helps activate the brain
Light enhances brain activity during a cognitive task even in some people who are totally blind, according to a study conducted by researchers at the University of Montreal and Boston’s Brigham and Women’s Hospital. The findings contribute to scientists’ understanding of everyone’s brains, as they also revealed how quickly light impacts on cognition. “We were stunned to discover that the brain still respond significantly to light in these rare three completely blind patients despite having absolutely no conscious vision at all,” said senior co-author Steven Lockley. “Light doesn’t just allow us to see, it tells the brain whether it’s night or day which in –turn ensures that our physiology, metabolism and behavior are synchronized with environmental time”. “For diurnal species like ours, light stimulates day-like brain activity, improving alertness and mood, and enhancing performance on many cognitive tasks,” explained senior co-author Julie Carrier. The results indicate that their brains can still “see”, or detect, light via a novel photoreceptor in the ganglion cell layer of the retina, different from the rods and cones we use to see.
Scientists believe, however, that these specialized photoreceptors in the retina also contribute to visual function in the brain even when cells in the retina responsible for normal image formation have lost their ability to receive or process light. A previous study in a single blind patient suggested that this was possible but the research team wanted to confirm this result in different patients. To test this hypothesis, the three participants were asked to say whether a blue light was on or off, even though they could not see the light. “We found that the participants did indeed have a non-conscious awareness of the light – they were able to determine correctly when the light was on greater than chance without being able to see it,” explained first author Gilles Vandewalle.
The next steps involved looking closely at what happened to brain activation when light was flashed at their eyes at the same time as their attentiveness to a sound was monitored. “The objective of this second test was to determine whether the light affected the brain patterns associated with attentiveness – and it did,” said first author Olivier Collignon.
Finally, the participants underwent a functional MRI brain scan as they performed a simple sound matching task while lights were flashed in their eyes. “The fMRI further showed that during an auditory working memory task, less than a minute of blue light activated brain regions important to perform the task. These regions are involved in alertness and cognition regulation as well being as key areas of the default mode network,” Vandewalle explained. Researchers believe that the default network is linked to keeping a minimal amount of resources available for monitoring the environment when we are not actively doing something. “If our understanding of the default network is correct, our results raise the intriguing possibility that light is key to maintaining sustained attention” agreed Lockley and Carrier. “This theory may explain why the brain’s performance is improved when light is present during tasks.”
(Source: nouvelles.umontreal.ca)
Recognising movement and its direction is one of the first and most important processing steps in any visual system. By this way, nearby predators or prey can be detected and even one’s own movements are controlled. More than fifty years ago, a mathematical model predicted how elementary motion detectors must be structured in the brain. However, which nerve cells perform this job and how they are actually connected remained a mystery. Scientists at the Max Planck Institute of Neurobiology in Martinsried have now come one crucial step closer to this “holy grail of motion vision”: They identified the cells that represent these so-called “elementary motion detectors” in the fruit fly brain. The results show that motion of an observed object is processed in two separate pathways. In each pathway, motion information is processed independently of one another and sorted according to its direction.
Ramón y Cajal, the famous neuroanatomist, was the first to examine the brains of flies. Almost a century ago, he thus discovered a group of cells he described as “curious elements with two tufts”. About 50 years later, German physicist Werner Reichardt postulated from his behavioural experiments with flies that they possess “elementary motion detectors”, as he referred to them. These detectors compare changes in luminance between two neighbouring photoreceptor units, or facets, in the fruit fly’s eye for every point in the visual space. The direction of a local movement is then calculated from this. At least, that is what the theory predicts. Since that time, the fruit fly research community has been speculating about whether these “two-tufted cells” described by Cajal are the mysterious elementary motion detectors.
The answer to this question has been slow in coming, as the tufted cells are extremely small – much too small for sticking an electrode into them and capturing their electrical signals. Now, Alexander Borst and his group at the Max Planck- Institute of Neurobiology have succeeded in making a breakthrough with the aid of a calcium indicator. These fluorescent proteins are formed by the neurons themselves and change their fluorescence when the cells are active. It thus finally became possible for the scientists to observe and measure the activity of the tufted cells under the microscope. The results prove that these cells actually are the elementary motion detectors predicted by Werner Reichardt.
As further experiments have shown, the tufted cells can be divided into two groups. One group (T4 cells) only reacts to a transition from dark to light caused by motion, while the other group (T5 cells) reacts oppositely – only for light-to-dark edges. In every group there are four subgroups, each of which only responds to movements in a specific direction – to the right, left, upwards or downwards. The neurons in these directionally selective groups release their information into layers of subsequent nerve tissue that are completely separated from one another. There, large neurons use these signals for visual flight control, generating the appropriate commands for the flight musculature, for example. This could be impressively proven by the scientists: When they blocked the T4 cells, the neurons connected downstream and the fruit flies themselves were shown in behavioural tests to be blind to motions caused by dark-to-light edges. When the T5 cells were blocked, light-to-dark edges could no longer be perceived.
In discussions about their research results, which have just been published in the scientific journal Nature, both lead authors, Matt Maisak and Jürgen Haag, were very impressed with the “cleanly differentiated, yet highly ordered” motion information within the brains of the fruit flies. Alexander Borst, head of the study, adds: “That was real teamwork – almost all of the members in my department took part in the experiments. One group carried out the calcium measurements, another worked on the electrophysiology, and a third made the behavioural measurements. They all pulled together. It was a wonderful experience.” And it should continue like this, since the scientists are already turning to the next mammoth challenge: they would now like to identify the neurons that deliver the input signals to the elementary motion detectors. According to Reichardt, the two signals coming from neighbouring photoreceptors in the eye have to be delayed in relation to one another. “That is going to be really exciting!” says Alexander Borst.
Switching night vision on or off
Neurobiologists at the Friedrich Miescher Institute have been able to dissect a mechanism in the retina that facilitates our ability to see both in the dark and in the light. They identified a cellular switch that activates distinct neuronal circuits at a defined light level. The switch cells of the retina act quickly and reliably to turn on and off computations suited specifically for vision in low and high light levels thus facilitating the transition from night to day vision. The scientists have published their results online in Neuron.
"It was fascinating to see how modern neurobiological methods allowed us to answer a question about vision that has been controversially discussed for the last 50 years", said Karl Farrow, postdoctoral fellow in Botond Roska’s group at the Friedrich Miescher Institute for Biomedical Research. Since the late 1950 scientists debated how the retina handles the different visual processes at low and high light intensities, at starlight and at daylight. Farrow and his colleagues have now identified a cellular switch in the retina that controls perception during these two settings.
At first glance, everything seems clear. The interplay of two photoreceptor types in the retina, the rods and the cones, allow us to see across a wide range of light intensities. The rods are highly sensitive and spring into action in the dark; the cones are activated during the day and in humans come in three diversities allowing us to see color. The rods help us detect objects during the night; while the cones allow us to discriminate the fine details of those objects during the day. The plethora of initial signals originating from the photoreceptors is computed in a system of only approximately 20 neuronal channels that transport information to the brain. The relay stations are the roughly 20 types of ganglion cells in the retina. How they manage the transition from light to dark and enable vision at the different light regimes has remained unclear.
In the retina several cell layers are stacked on top of each other. The photoreceptors are the first to be activated by light; they relay the information to bipolar cells, which in turn activate ganglion cells. The different types of ganglion cells take on distinct tasks during vision. These ganglion cells are embedded in a mesh of amacrine cells that modulate their activity. “Here is where our new genetic tools proofed very helpful,” said Farrow, “because they allowed us to look at individual ganglion cell types and to specifically measure their activities at different light intensities.” Farrow and colleagues could thus show that the activity of one particular type of ganglion cells, called PV1, is modulated like a switch by amacrine cells. The amacrine cells inhibit the ganglion cell strongly at high light intensities and weakly at low ambient light levels. This switch is abrupt and reversible and it occurs at the light intensities where cones are starting to be activated. “We were surprised to see how fast this switch occurs and how reliable we were able to switch between the two states at defined light intensities”, comments Farrow.
While the above experiments were done in a mouse model, the FMI neurobiologists could show that a similar switch operates in human vision. Their volunteers had to look at narrow and broader stripes at different light levels. They could show that there again a switch operates. While the general ability to see all striped patterns improved with increasing light intensity, suddenly, at a certain light level, the volunteers were much better able to detect thinner patterns as compared to the broader ones. Interestingly enough this switch happened at precisely the light level where the volunteers were also able to discriminate between red and blue, hence where the cones spring into action. “We think we have found a regulatory principle that could apply to several processes in the brain”, said Roska, “This principle could explain some situations when gradual changes in the sensory environment leads to abrupt changes in brain computations and perception”
(Source: medicalxpress.com)
Farsighted engineer invents bionic eye to help the blind
For UCLA bioengineering professor Wentai Liu, more than two decades of visionary research burst into the headlines last month when the FDA approved what it called “the first bionic eye for the blind.”
The Argus II Retinal Prosthesis System — developed by a team of physicians and engineers from around the country — aids adults who have lost their eyesight due to retinitis pigmentosa (RP), age-related macular degeneration or other eye diseases that destroy the retina’s light-sensitive photoreceptors.
At the heart of the device is a tiny yet powerful computer chip developed by Liu that, when implanted in the retina, effectively sidesteps the damaged photoreceptors to “trick” the eye into seeing. The Argus II operates with a miniature video camera mounted on a pair of eyeglasses that sends information about images it detects to a microprocessor worn on the user’s waistband. The microprocessor wirelessly transmits electronic signals to the computer chip, a fingernail-size grid made up of 60 circuits. These chips stimulate the retina’s nerve cells with electronic impulses which head up the optic nerve to the brain’s visual cortex. There, the brain assembles them into a composite image.
Recipients of the retinal implant can read oversized letters of the alphabet, discern objects and movement, and even see the outlines and some details of faces. And while the picture is far from perfect — the healthy human eye sees at a much higher resolution — it’s a breakthrough for people like the first patient, a man in his 70s who was blinded at age 20 by RP, to receive the implant in clinical trials. “It was the first time he’d seen light in a half-century,” said Liu, adding that “it feels good as the engineer” to have helped make this possible.
Liu joined the Artificial Retina Project in 1988 as a professor of computer and electrical engineering at North Carolina State University. The multidisciplinary research project was funded by the U.S. Department of Energy’s Office of Science because it envisioned a potential pandemic of eyesight loss in America’s aging population. Leading the project was Duke University ophthalmologist and neurosurgeon Dr. Mark Humayun, now on faculty at USC. He tapped Liu to engineer the artificial retina.
“I thought it was a great idea,” Liu said. “But I asked, ‘What can I do?’ because I didn’t know much about biology.” Humayun handed him a six-inch-thick medical manual on the retina. “The learning curve was very steep,” Liu recalled with a laugh.
However, Liu’s fellow engineers questioned his sanity. “I was working on integrated chip design and had just gotten tenure when I signed on to this project. They said, ‘You’re crazy!’ But I’m glad I made that choice, getting into this new field.”
Study Sheds Light on the Complexity of Gene Therapy for Congenital Blindness
Independent clinical trials, including one conducted at the Scheie Eye Institute at the Perelman School of Medicine, have reported safety and efficacy for Leber congenital amaurosis (LCA), a congenital form of blindness caused by mutations in a gene (RPE65) required for recycling vitamin A in the retina. Inherited retinal degenerative diseases were previously considered untreatable and incurable. There were early improvements in vision observed in the trials, but a key question about the long-term efficacy of gene therapy for curing the retinal degeneration in LCA has remained unanswered. Now, new research from the Scheie Eye Institute, published this week in the Proceedings of the National Academy of Sciences, finds that gene therapy for LCA shows enduring improvement in vision but also advancing degeneration of affected retinal cells, both in LCA patients and animal models of the same condition.
LCA disease from RPE65 mutations has two-components: a biochemical blockade leading to impaired vision, and a progressive loss of the light-sensing photoreceptor cells throughout life of the affected patient. The authors of the new study explain that until now gene therapy has been optimistically assumed, but not proven, to solve both disease components at the same time.
“We all hoped that the gene injections cured both components – re-establishing the cycle of vision and also preventing further loss of cells to the second disease component” said Artur V. Cideciyan, PhD, lead author and co-investigator of an LCA clinical trial at Penn.
Yet, when the otherwise invisible cell layers of the retina were measured by optical imaging in clinical trial participants serially over many years, the rate of cell loss was the same in treated and untreated regions. “In other words, gene therapy improved vision but did not slow or halt the progression of cell loss,” commented Cideciyan.
“These unexpected observations should help to advance the current treatment by making it better and longer lasting,” commented co-author Samuel G. Jacobson, MD, PhD, principal investigator of the clinical trial. “Slowing cell loss in different retinal degenerations has been a major research direction long before the current gene therapy trials. Now, the two directions must converge to ensure the longevity of the beneficial visual effects in this form of LCA.”
(Image: bigstockphoto)