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Braithwaite T.,Moorfields Eye Hospital NHS Foundation Trust | Holder G.E.,Moorfields Eye Hospital NHS Foundation Trust | Holder G.E.,UCL Institute of Ophthalmology | Lee R.W.J.,Moorfields Eye Hospital NHS Foundation Trust | And 6 more authors.
Autoimmunity Reviews | Year: 2014

The term autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that affect retinal function, often but not exclusively at the level of the photoreceptor. They typically present with painless visual loss, which may be accompanied by normal fundus examination. Some are progressive, often rapidly. They present a diagnostic challenge because there are no standardised clinical or laboratory based diagnostic criteria. Included within the spectrum are cancer-associated retinopathy, melanoma-associated retinopathy and presumed non-paraneoplastic autoimmune retinopathy. Differentiation from other retinopathies can be challenging, with overlap in symptoms, signs, and investigation findings, and an absence of pathognomonic features. However, technological developments in ophthalmic imaging and serological investigation over the past decade are adding novel dimensions to the investigation and classification of patients with these rare diseases. This review addresses the clinical, imaging, and serological features of the autoimmune retinopathies, and discusses the relative strengths and limitations of candidate diagnostic features. © 2014 Elsevier B.V.


Murphy S.E.,UCL Institute of Ophthalmology | Levine T.P.,UCL Institute of Ophthalmology
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2016

Dysfunction of VAMP-associated protein (VAP) is associated with neurodegeneration, both Amyotrophic Lateral Sclerosis and Parkinson's disease. Here we summarize what is known about the intracellular interactions of VAP in humans and model organisms. VAP is a simple, small and highly conserved protein on the cytoplasmic face of the endoplasmic reticulum (ER). It is the sole protein on that large organelle that acts as a receptor for cytoplasmic proteins. This may explain the extremely wide range of interacting partners of VAP, with components of many cellular pathways binding it to access the ER. Many proteins that bind VAP also target other intracellular membranes, so VAP is a component of multiple molecular bridges at membrane contact sites between the ER and other organelles. So far approximately 100 proteins have been identified in the VAP interactome (VAPome), of which a small minority have a "two phenylalanines in an acidic tract" (FFAT) motif as it was originally defined. We have analyzed the entire VAPome in humans and yeast using a simple algorithm that identifies many more FFAT-like motifs. We show that approximately 50% of the VAPome binds directly or indirectly via the VAP-FFAT interaction. We also review evidence on pathogenesis in genetic disorders of VAP, which appear to arise from reduced overall VAP levels, leading to ER stress. It is not possible to identify one single interaction that underlies disease. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim Levine and Anant K. Menon. © 2016 Elsevier B.V.


McClenaghan F.C.,Barts and the London NHS Foundation Trust | Ezra D.G.,Moorfields Eye Hospital NHS Foundation Trust | Ezra D.G.,UCL Institute of Ophthalmology | Ezra D.G.,University College London | Holmes S.B.,Barts and the London NHS Foundation Trust
Current Opinion in Ophthalmology | Year: 2011

PURPOSE OF REVIEW: To examine the proposed mechanisms of vision-threatening injuries occurring secondary to orbital and facial trauma: traumatic optic neuropathy (TON), retrobulbar haemorrhage (RBH) and penetrating eye injury. To evaluate the evidence supporting different management options for traumatic vision-threatening injury. RECENT FINDINGS: Despite considerable debate over the roles of surgical decompression and systemic steroid therapy for TON, these interventions have not been proved to be more effective than conservative management and there is limited evidence that the use of steroids may be associated with an adverse outcome. Lateral canthotomy and inferior cantholysis have been proven to be effective treatments for RBH. Orbital exploration and surgical evacuation of haematoma remains a second line intervention. Open globe injuries require immediate primary surgical exploration and repair. Irretrievable devastating globe injuries require either enucleation or evisceration. There is no consensus as to which is the best treatment with recent surveys indicating that enucleation is preferred in the USA and evisceration in the United Kingdom. SUMMARY: Conservative management is the first line treatment for TON. The evidence strongly supports lateral canthotomy and inferior cantholysis as best treatment for RBH. There is no consensus as to whether enucleation or evisceration is the best treatment for irretrievable devastating globe injury. The choice of management is currently determined by surgeon preference. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


News Article | November 9, 2016
Site: www.sciencedaily.com

Blood vessels play a vital role in stem cell reproduction, enabling the brain to grow and develop in the womb, reveals new UCL research in mice. The study, published in the Proceedings of the National Academy of Sciences and funded by Wellcome, shows that blood vessels can increase the number of neural stem cells inside a living organism. This could be important for the design of stem cell-based therapies that aim to regenerate diseased or damaged parts of the nervous system. In the developing brain, new neurons are produced by neural stem cells in 'neurogenic' areas, where they have to be instructed when and how often they should divide or what type of progeny they should produce. Until now, however, the signals responsible for these instructions have remained elusive. "We found that blood vessels play a vital role in telling neural stem cells when and how to reproduce," explains lead author Mathew Tata (UCL Institute of Ophthalmology). "We examined neural stem cell behaviour in the brainstem of mice lacking the blood vessel protein NRP1, because this part of the brain is particularly important to control fundamental processes such as breathing and heart rate. Preventing blood vessel growth in the neurogenic areas of the brainstem interfered with normal neuron production, causing neural stem cells to lose their ability to reproduce. As a result the stem cells disappeared from the brainstem before its growth was complete, so mice lacking NRP1 ended up with smaller brainstems." The research provides the first evidence that blood vessels are not only important for delivering blood to the developing brain, but also play an important role in stem cell signalling. "Blood vessels are best known for their important function in supplying oxygen and nutrients to the brain," says senior author Christiana Ruhrberg (UCL Institute of Ophthalmology). "However, the most intriguing finding of this study was that blood vessels did not regulate neural stem cell behaviour in the brainstem simply through their role in brain oxygenation or keeping brain tissue healthy. We found that blood vessels also provide important signals that allow stem cells to reproduce for a longer period of time, before they permanently become nerve cells that cannot multiply."


News Article | February 5, 2016
Site: www.rdmag.com

Under standing the textures and patterns of pancakes is helping UCL scientists improve surgical methods for treating glaucoma. The appearance of pancakes depends on how water escapes the batter mix during the cooking process and this varies with the thickness of the batter, according to new UCL research. Understanding the physics of the process can help perfect pancake making and gives important insights into how flexible sheets, like those found in human eyes, interact with flowing vapor and liquids. Co-author Professor Ian Eames, Professor of Fluid Mechanics at UCL Engineering, said: "Pancakes come in many shapes and sizes and everyone has their favorites - some prefer a small, thick pancake with a smooth surface whereas others enjoy a large, thin crêpe with 'craters' and crispy edges. We've discovered that the variations in texture and patterns result from differences in how water escapes the batter during cooking and that this is largely dependent on the thickness and spread of the batter." The study, published in Mathematics TODAY, compared recipes for 14 different types of pancakes from across the world including the Canadian ploye and Malaysian lempeng kelapa. For each, the team analyzed and plotted the aspect ratio, i.e. the pancake diameter to the power of three in relation to its volume of batter, and the baker's percentage which is the ratio of liquid to flour in the batter, i.e. the thickness of the batter. They found thick, almost spherical pancakes such as Dutch poffertjes had the lowest aspect ratio at 3, whereas large, thin French crêpes had the biggest at 300. The baker's percentage didn't vary as dramatically, ranging from 100 for thick mixtures (i.e. equal measures of flour and liquid) to 175 for thinner mixtures containing more liquid. To explore how these ratios influence the textures and patterns of pancakes, the scientists made batters with a fixed amount of flour and egg but different amounts of milk. Pancakes were made using the batters in the same pan, at the same heat and without fat. The scientists found that: "We found that the physics of pancake cooking is complex but generally follows one of two trends. If the batter spreads easily in the pan, the pancake ends up with a smooth surface pattern and less burning as the vapor flow buffers the heat of the pan. We found a thin pancake can only be created by physically spreading the batter across the pan and in this case, the vapor tends to escape through channels or diffusion," said co-author Yann Bouremel, UCL Institute of Ophthalmology. "We work on better surgical methods for treating glaucoma, which is a build-up of pressure in eyes caused by fluid. To treat this, surgeons create an escape route for the fluid by carefully cutting the flexible sheets of the sclera. We are improving this technique by working with engineers and mathematicians. It's a wonderful example of how the science of everyday activities can help us with the medical treatments of the future," said Peng Khaw, Director of the NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology. Read more at: "We work on better surgical methods for treating glaucoma, which is a build-up of pressure in eyes caused by fluid. To treat this, surgeons create an escape route for the fluid by carefully cutting the flexible sheets of the sclera. We are improving this technique by working with engineers and mathematicians. It's a wonderful example of how the science of everyday activities can help us with the medical treatments of the future."Read more at: http://phys.org/news/2016-02-physics-pancake-sight.html#jCp


News Article | November 8, 2016
Site: www.biosciencetechnology.com

Blood vessels play a vital role in stem cell reproduction, enabling the brain to grow and develop in the womb, reveals new UCL research in mice. The study, published in the Proceedings of the National Academy of Sciences and funded by Wellcome, shows that blood vessels can increase the number of neural stem cells inside a living organism. This could be important for the design of stem cell-based therapies that aim to regenerate diseased or damaged parts of the nervous system. In the developing brain, new neurons are produced by neural stem cells in 'neurogenic' areas, where they have to be instructed when and how often they should divide or what type of progeny they should produce. Until now, however, the signals responsible for these instructions have remained elusive. "We found that blood vessels play a vital role in telling neural stem cells when and how to reproduce," explains lead author Mathew Tata (UCL Institute of Ophthalmology). "We examined neural stem cell behaviour in the brainstem of mice lacking the blood vessel protein NRP1, because this part of the brain is particularly important to control fundamental processes such as breathing and heart rate. Preventing blood vessel growth in the neurogenic areas of the brainstem interfered with normal neuron production, causing neural stem cells to lose their ability to reproduce. As a result the stem cells disappeared from the brainstem before its growth was complete, so mice lacking NRP1 ended up with smaller brainstems." The research provides the first evidence that blood vessels are not only important for delivering blood to the developing brain, but also play an important role in stem cell signalling. "Blood vessels are best known for their important function in supplying oxygen and nutrients to the brain," says senior author Christiana Ruhrberg (UCL Institute of Ophthalmology). "However, the most intriguing finding of this study was that blood vessels did not regulate neural stem cell behaviour in the brainstem simply through their role in brain oxygenation or keeping brain tissue healthy. We found that blood vessels also provide important signals that allow stem cells to reproduce for a longer period of time, before they permanently become nerve cells that cannot multiply."


News Article | November 7, 2016
Site: www.eurekalert.org

Blood vessels play a vital role in stem cell reproduction, enabling the brain to grow and develop in the womb, reveals new UCL research in mice. The study, published in the Proceedings of the National Academy of Sciences and funded by Wellcome, shows that blood vessels can increase the number of neural stem cells inside a living organism. This could be important for the design of stem cell-based therapies that aim to regenerate diseased or damaged parts of the nervous system. In the developing brain, new neurons are produced by neural stem cells in 'neurogenic' areas, where they have to be instructed when and how often they should divide or what type of progeny they should produce. Until now, however, the signals responsible for these instructions have remained elusive. "We found that blood vessels play a vital role in telling neural stem cells when and how to reproduce," explains lead author Mathew Tata (UCL Institute of Ophthalmology). "We examined neural stem cell behaviour in the brainstem of mice lacking the blood vessel protein NRP1, because this part of the brain is particularly important to control fundamental processes such as breathing and heart rate. Preventing blood vessel growth in the neurogenic areas of the brainstem interfered with normal neuron production, causing neural stem cells to lose their ability to reproduce. As a result the stem cells disappeared from the brainstem before its growth was complete, so mice lacking NRP1 ended up with smaller brainstems." The research provides the first evidence that blood vessels are not only important for delivering blood to the developing brain, but also play an important role in stem cell signalling. "Blood vessels are best known for their important function in supplying oxygen and nutrients to the brain," says senior author Christiana Ruhrberg (UCL Institute of Ophthalmology). "However, the most intriguing finding of this study was that blood vessels did not regulate neural stem cell behaviour in the brainstem simply through their role in brain oxygenation or keeping brain tissue healthy. We found that blood vessels also provide important signals that allow stem cells to reproduce for a longer period of time, before they permanently become nerve cells that cannot multiply."


News Article | February 6, 2016
Site: motherboard.vice.com

Somewhere on University College London’s campus there is a lab occupied by a number of engineers making breakfast. The only thing on the menu in this lab is pancakes, and many of the chefs have terminal degrees in fluid mechanics. Everyone in the lab is possessed with a singular purpose: creating the perfect flapjack. Few would disagree that this is an admirable goal, but the engineers’ maniacal pursuit of pancake perfection has less to do with ensuring a delicious breakfast than figuring out what the physics of pancakes can teach us about restoring eyesight. As the UCL team details in the current issue of Mathematics TODAY, figuring out the physics involved in cooking pancakes could help improve surgical methods for treating glaucoma, a group of eye diseases that can lead to total or partial loss of vision. By looking at pancake recipes from around the world, ranging from Canadian ploye to Dutch poffertjes to Malaysian lempeng kelapa, the team sought to study how the texture and appearance of the pancakes varied by recipe. According to the UCL team’s research, the appearance of pancakes largely depends on how water escapes from the batter during cooking, a factor which is itself influenced by the thickness of the batter. To arrive at this conclusion, the team analyzed two parameters of each of the 14 pancake recipes. First they looked at the cake’s aspect ratio (the pancake’s diameter raised by a power of three in relation to the volume of its batter), and then the “baker’s percentage” (the ratio of liquid to flour in the batter, which determines the batter’s thickness). What the team found was that small, thick pancakes like Dutch poffertjes had the lowest aspect ratios (3) whereas large, thin pancakes like French crêpes had the largest aspect ratios (300). The baker’s percentages didn’t have such wild variations, staying in a range of 100 (thick batters with an equal amount of liquid and flour) to 225 (runny mixtures with significantly more liquid than flour). By maintaining a fixed amount of egg and flour in different batter recipes, the UCL team experimented with different amounts of milk to see how the baker’s percentages would affect the appearance of the flapjacks. They found that thicker batters with a baker’s ratio of around 100 led to pancakes with irregular craters on the bottom surface because water vapors were trapped in the cooking process and would unevenly raise the pancake from the pan. The thinnest batters with baker’s ratios of 225 were found to have even color surfaces pockmarked with darker spots and a distinctive dark outer ring around the edge of the pancake where the batter was thinnest. Water vapor escapes smoothly across the bottom of the pancake, leaving a uniform color and small channels where the water vapor escaped. Small channels where water vapor escaped can be seen on pancakes Image: Rob Eagle, UCL "We found that the physics of pancake cooking is complex, but generally follows one of two trends,” Yann Bouremel, a co-author of the study at the UCL Institute of Ophthalmology, said in a press release. “If the batter spreads easily in the pan, the pancake ends up with a smooth surface pattern and less burning as the vapor flow buffers the heat of the pan. We found a thin pancake can only be created by physically spreading the batter across the pan and in this case, the vapor tends to escape through channels or diffusion." According to the team, the observations provide valuable insight into how flexible sheets, like those found in the human eye, interact with flowing vapor and liquid. This is of particular use in figuring out new ways to treat glaucoma, a group of diseases which is characterized by the buildup of liquid around the eye. This liquid is unable to escape and puts pressure on the optic nerve, and overtime this pressure causes damage that can lead to partial or total blindness. Thus, figuring out a way to allow this liquid to escape (say, by studying the way liquid escapes pancake batter) could save people’s eyesight. “To treat [glaucoma], surgeons create an escape route for the fluid by carefully cutting the flexible sheets of the sclera,”Professor Sir Peng Khaw, co-author and Director of the NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, said . “We are improving this technique by working with engineers and mathematicians. [The pancakes study] is a wonderful example of how the science of everyday activities can help us with the medical treatments of the future."


News Article | November 15, 2016
Site: www.eurekalert.org

Treating bees with light therapy can counteract the harmful effects of neonicotinoid pesticides and improve survival rates of poisoned bees, finds a new UCL study Treating bees with light therapy can counteract the harmful effects of neonicotinoid pesticides and improve survival rates of poisoned bees, finds a new UCL study. "Neonicotinoid pesticides are a persistent threat to global bee populations, which play a critical role in agriculture," says Professor Glen Jeffery (UCL Institute of Ophthalmology), the senior author of the PLOS ONE paper. "My team is working to develop a small device that can be fitted into a commercial hive, which could be an economic solution to a problem with very widespread implications." The pesticides undermine mitochondrial function and compromise the production of ATP, the currency for energy that drives cellular function. This results in reduced mobility among bees exposed to neonicotinoids, leading them to die of starvation, unable to feed themselves. The researchers used four groups of bees from commercial hives, with more than 400 bees in each colony. Two groups were exposed to a neonicotinoid, Imidacloprid, for ten days, with one group also being treated with light therapy over the same period - 15 minutes of near infrared light (670nm) was shone into the hive twice daily. The mobility of the bees that were poisoned but not treated with light therapy dropped off rapidly, as did their ATP levels, and their survival rate declined accordingly. The bees that were poisoned but also treated with light therapy had significantly better mobility and survival rates, living just as long and functioning just as well as bees that had not been poisoned. One group was given light therapy without being poisoned, and their survival rate was even better than the control group. The researchers found the deep red light did not interfere with bee behaviour as they cannot see it. "Long-wavelength light treatments have been shown in other studies to reduce mitochondrial degeneration which results from aging processes. It's beneficial even for bees that aren't affected by pesticides, so light therapy can be an effective means of preventing loss of life in case a colony becomes exposed to neonicotinoids. It's win-win," Professor Jeffery says. While light therapy works best as a preventative measure, the researchers found it can also be helpful as treatment in response to an incident of pesticide exposure, as long as the treatment is started within a couple days of exposure. "We found that by shining deep red light on the bee which had been affected by the toxic pesticides that they could recover, as it improved mitochondrial and visual function, and enabled them to move around and feed again," says Dr Michael Powner (City, University of London), who led the study while at UCL. Researchers at UCL Ophthalmology have been studying near-infrared light therapy because of its benefits not only for bees, but also for other animals including humans, particularly to counteract effects of aging and a range of neurological diseases. "When a nerve cell is using more energy than other cells, or is challenged because of a lack of energy, red light therapy can give it a boost by improving mitochondrial function. Essentially, it recharges the cell's batteries," Professor Jeffery explains. The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).


News Article | November 15, 2016
Site: phys.org

"Neonicotinoid pesticides are a persistent threat to global bee populations, which play a critical role in agriculture," says Professor Glen Jeffery (UCL Institute of Ophthalmology), the senior author of the PLOS ONE paper. "My team is working to develop a small device that can be fitted into a commercial hive, which could be an economic solution to a problem with very widespread implications." The pesticides undermine mitochondrial function and compromise the production of ATP, the currency for energy that drives cellular function. This results in reduced mobility among bees exposed to neonicotinoids, leading them to die of starvation, unable to feed themselves. The researchers used four groups of bees from commercial hives, with more than 400 bees in each colony. Two groups were exposed to a neonicotinoid, Imidacloprid, for ten days, with one group also being treated with light therapy over the same period - 15 minutes of near infrared light (670nm) was shone into the hive twice daily. The mobility of the bees that were poisoned but not treated with light therapy dropped off rapidly, as did their ATP levels, and their survival rate declined accordingly. The bees that were poisoned but also treated with light therapy had significantly better mobility and survival rates, living just as long and functioning just as well as bees that had not been poisoned. One group was given light therapy without being poisoned, and their survival rate was even better than the control group. The researchers found the deep red light did not interfere with bee behaviour as they cannot see it. "Long-wavelength light treatments have been shown in other studies to reduce mitochondrial degeneration which results from aging processes. It's beneficial even for bees that aren't affected by pesticides, so light therapy can be an effective means of preventing loss of life in case a colony becomes exposed to neonicotinoids. It's win-win," Professor Jeffery says. While light therapy works best as a preventative measure, the researchers found it can also be helpful as treatment in response to an incident of pesticide exposure, as long as the treatment is started within a couple days of exposure. "We found that by shining deep red light on the bee which had been affected by the toxic pesticides that they could recover, as it improved mitochondrial and visual function, and enabled them to move around and feed again," says Dr Michael Powner (City, University of London), who led the study while at UCL. Researchers at UCL Ophthalmology have been studying near-infrared light therapy because of its benefits not only for bees, but also for other animals including humans, particularly to counteract effects of aging and a range of neurological diseases. "When a nerve cell is using more energy than other cells, or is challenged because of a lack of energy, red light therapy can give it a boost by improving mitochondrial function. Essentially, it recharges the cell's batteries," Professor Jeffery explains. Explore further: Impact of pesticide on bumblebees revealed by taking experiments into the field

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