̽��ֱ�� of Cambridge - eye

Technique to regenerate the optic nerve offers hope for future glaucoma treatment

cjb250 — Thu, 05 Nov 2020 10:00:30 +0000

Axons – nerve fibres – in the adult central nervous system (CNS) do not normally regenerate after injury and disease, meaning that damage is often irreversible. However, over the past decade there have been a number of discoveries that suggest it may be possible to stimulate regeneration.

In a study published today in Nature Communications, scientists tested whether the gene responsible for the production of a protein known as Protrudin could stimulate the regeneration of nerve cells and protect them from cell death after an injury.

̽��ֱ��team, led by Dr Richard Eva, Professor Keith Martin and Professor James Fawcett from the John van Geest Centre for Brain Repair at the ̽��ֱ�� of Cambridge, used a cell culture system to grow brain cells in a dish. They then injured their axons using a laser and analysed the response to this injury using live-cell microscopy. ̽��ֱ��researchers found that increasing the amount or activity of Protrudin in these nerve cells vastly increased their ability to regenerate.

Nerve cells in the retina, known as retinal ganglion cells, extend their axons from the eye to the brain through the optic nerve in order to relay and process visual information. To investigate whether Protrudin might stimulate repair in the injured CNS in an intact organism, the researchers used a gene therapy technique to increase the amount and activity of Protrudin in the eye and optic nerve. When they measured the amount of regeneration a few weeks after a crush injury to the optic nerve, the team found that Protrudin had enabled the axons to regenerate over large distances. They also found that the retinal ganglion cells were protected from cell death.

̽��ֱ��researchers showed that this technique may help protect against glaucoma, a common eye condition. In glaucoma, the optic nerve that connects the eye to the brain is progressively damaged, often in association with elevated pressure inside the eye. If not diagnosed early enough, glaucoma can lead to loss of vision. In the UK, round one in 50 people over the age of 40, and one in ten people over the age of 75 is affected by glaucoma.

To demonstrate this protective effect of Protrudin against glaucoma, the researchers used a whole retina from a mouse eye and grew it in a cell-culture dish. Usually around a half of retinal neurons die within three days of retinal removal, but the researchers found that increasing or activating Protrudin led to almost complete protection of retinal neurons.

Dr Veselina Petrova from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge, the study’s first author, said: “Glaucoma is one of leading causes of blindness worldwide. ̽��ֱ��causes of glaucoma are not completely understood, but there is currently a large focus on identifying new treatments by preventing nerve cells in the retina from dying, as well as trying to repair vision loss through the regeneration of diseased axons through the optic nerve.

“Our strategy relies on using gene therapy – an approach already in clinical use – to deliver Protrudin into the eye. It’s possible our treatment could be further developed as a way of protecting retinal neurons from death, as well as stimulating their axons to regrow. It’s important to point out that these findings would need further research to see if they could be developed into effective treatments for humans.”

Protrudin normally resides within the endoplasmic reticulum, tiny structures within our cells. In this study, the team showed that the endoplasmic reticulum found in axons appears to provide materials and other cellular structures important for growth and survival in order to support the process of regeneration after injury. Protrudin stimulates transport of these materials to the site of injury.

Dr Petrova added: “Nerve cells in the central nervous system lose the ability to regenerate their axons as they mature, so have very limited capacity for regrowth. This means that injuries to the brain, spinal cord and optic nerve have life-altering consequences.

“ ̽��ֱ��optic nerve injury model is often used to investigate new treatments for stimulating CNS axon regeneration, and treatments identified this way often show promise in the injured spinal cord. It’s possible that increased or activated Protrudin might be used to boost regeneration in the injured spinal cord.”

̽��ֱ��research was supported by the Medical Research Council, Fight for Sight, the Bill and Melinda Gates Foundation, Cambridge Eye Trust and the National Eye Research Council.

Reference
Petrova, V et al. Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS. Nat Comms; 5 Nov 2020; DOI: 10.1038/s41467-020-19436-y

Scientists have used gene therapy to regenerate damaged nerve fibres in the eye, in a discovery that could aid the development of new treatments for glaucoma, one of the leading causes of blindness worldwide.

It’s possible our treatment could be further developed as a way of protecting retinal neurons from death, as well as stimulating their axons to regrow

Veselina Petrova

TobiasD

Eye

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̽��ֱ��amazing axon adventure

sc604 — Fri, 05 Feb 2016 09:45:21 +0000

To read these words, light is first refracted by the cornea, through the pupil in the iris and onto the lens, which focuses images onto the retina. ̽��ֱ��images are received by light-sensitive cells in the retina, which transmit impulses to the brain. These impulses are carried by a set of neurons called the retinal ganglion cells. Once the impulses reach the brain, the brain then has to piece together the information it receives into an understandable image. All of this happens in a fraction of a second.

Information travels from the retina to the brain via axons – the long, threadlike parts of neurons – sent out by the retinal ganglion cells. During embryonic development, axons are sent out to find their specific targets in the brain, so that images can be processed.

For an axon in a growing embryo, the journey from retina to brain is not a straightforward one. It’s a very long way for a tiny axon, through a constantly changing series of environments that it has never encountered before. So how do axons know where to go, and what can it tell us about how the brain is made and maintained?

Two ̽��ֱ�� of Cambridge researchers, Professor Christine Holt of the Department of Physiology, Development and Neuroscience, and Dr Stephen Eglen of the Department of Applied Mathematics and Theoretical Physics, are taking two different, but complementary, approaches to these questions.

With funding from the European Research Council and the Wellcome Trust, Holt’s research group is aiming to better understand the molecular and cellular mechanisms that guide and maintain axon growth, which in turn will aid better understanding of how nerve connections are first established.

“It’s an impressive navigational feat,” says Holt. “ ̽��ֱ��pathway between the retina and the brain may look homogeneous, but in reality it’s like a patchwork quilt of different molecular domains.”

On the pathway through this patchwork quilt, there is a set of distinct beacons, breaking the axon’s journey down into separate steps. Every time the growing axon reaches a new beacon, it has to make a decision about which way to go. At the tip of the axon is a growth cone, which ‘sniffs out’ certain chemical signals emitted from the beacons, helping it to steer in the right direction.

̽��ֱ��growth cones are receptive to certain signals and blind to others, so depending on what the axon encounters when it reaches a particular beacon, it will behave in a certain way. Holt’s research group uses a variety of techniques to determine what the signals are at the steering points where axons alter their direction of growth or their behaviour, such as the optic chiasm where certain axons cross to the opposite side of the brain, or at the point where they first leave the eye.

While Holt uses experiments to understand the development of the visual system, Eglen uses mathematical models as a complementary technique to try to answer the same questions.

“You’ve got much more freedom in a theoretical model than you do in an experiment,” he says. “A common experimental approach is to remove something genetically and see what happens. I think of that a little like taking the battery out of your car. Doing that will tell you that the battery is necessary for the car to function, but it doesn’t really tell you why.”

Theoretical models allow researchers to approach the questions around neural development from a different angle. To capture the essence of the neural system, they try to represent the building blocks of development and see what kind of behaviour would result.

But no model yet can fully capture the complexities of how the visual system develops, which Eglen views not only as a challenge for him as a mathematician, but also as a challenge back to the experimental community.

“It had been thought that if we built a model and took out all of the guidance molecules, there would be no topographic order whatsoever,” says Eglen. “But instead we found that there is still residual order in how the neurons are wired up, so there must be extra molecules or mechanisms that we don’t know about. What we’re trying to do is to take biology and put it into computers so that we can really test it.”

“In the past 15–20 years, there’s been a revolution in terms of being able to identify the specific molecules that act as guidance receptors or signals, but there’s still so much we don’t yet know, which is why we’re using both theoretical and experimental techniques to answer these questions,” says Holt. “And in addition to this question of wiring, we’re also looking at the problem of mapping – how do the terminal ends of the axons find their ultimate destination in the brain?”

Holt’s group has found that the same guidance molecule can have different roles depending on what aspect of growth is going on – but the question then becomes how do you wire the brain with so few molecules?

Adding to the complexity was another puzzling discovery – that the growth cones of axons can make proteins. Previous knowledge held that new proteins could be synthesised only within the main cellular part of each neuron, the cell body (where the nucleus is located), and then transported into axons. However, Holt’s group found that the growth cones of axons are also capable of synthesising proteins ‘on demand’ when they encounter new guidance beacons, suggesting that messenger RNA (mRNA) molecules play a role in helping axons to navigate to their correct destinations. mRNAs are the molecules from which new proteins are synthesised, and further experiments found that axons contain hundreds or even thousands of different types of this nuclear material.

In addition to their role in axon growth when the brain is wiring itself up during development, certain types of mRNA are also important in maintaining the connections in the adult brain, by keeping mitochondria – the energy-producing ‘batteries’ of cells – healthy, which, in turn, keeps axons healthy.

“It is a whole new view to the idea of degeneration in later life – a lot of different components have to work together to get local protein synthesis to work, so if just one of those components fails, degeneration can occur,” says Holt. “We’ve also found that many of the types of mRNA that are being translated in axons are the same ones that you see in diseases like Huntingdon’s and Parkinson’s, so basic knowledge of this sort is essential for the development of clinical therapies in nerve repair and for understanding these and other neurodegenerative disorders.”

How does the brain make connections, and how does it maintain them? Cambridge neuroscientists and mathematicians are using a variety of techniques to understand how the brain ‘wires up’, and what it might be able to tell us about degeneration in later life.

It’s an impressive navigational feat. ̽��ֱ��pathway between the retina and the brain may look homogeneous, but in reality it’s like a patchwork quilt.

Christine Holt

K-M. Leung

A growing axon tip exhibits polarised mRNA translation (red)

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Lifelong learning and the plastic brain

lw355 — Wed, 19 Nov 2014 10:06:56 +0000

When a group of experimental psychologists moved into their new lab space in Cambridge earlier this year, they took a somewhat unconventional approach to refurbishing their tea room: they had the walls tiled with the Café Wall Illusion.

̽��ֱ��illusion, so-named after it was spotted on the wall of a Bristol café in the 1970s, is a much-debated geometrical trick of the eye and brain in which perfectly parallel lines of black and white tiles appear wedge-shaped and sloped.

It’s also an excellent demonstration of how the brain interprets the world in a way that moves beyond what the input is from the eye, as one of the experimental psychologists, Professor Zoe Kourtzi, explained. “In interpreting the world around us, our brains are challenged by a plethora of information. ̽��ֱ��brain is thought to integrate information from multiple sources and solve the puzzle of perception by taking into account not only the signals registered by the sensory organs but also their context in space and time.

“In the Café Wall Illusion, the brain takes into account the surrounding tiles, but it also relies on our previous knowledge acquired through training and experience when interpreting a new situation.”

From the day we are born, neurons in the brain start to make connections that combine what we can see, hear, taste, touch and smell with our experiences and memories. Neuroscientists refer to the brain’s ‘plasticity’ in explaining this ability to restructure and learn new things, continually building on previous patterns of neuronal interactions.

To unravel the mechanisms that underlie how brains learn, Kourtzi’s team is looking at how brains recognise objects in a cluttered scene. “This aspect is vital for successful interactions in our complex environments,” she explained. “It’s how we recognise a face in a crowd or a landmark during navigation.”

Visual perception is also highly trainable. ̽��ֱ��brain can use previous experience of similar cues to be quicker at identifying the image from the ‘noise’ – the proverbial needle from the haystack.

But although neuroscientists recognise that this type of brain plasticity is fundamental to our ability to cope with continually changing settings at home, school, work and play, little is known about how we can stimulate our brain to enhance this learning process, right across the life span.

“ ̽��ֱ��process of ‘learning to learn’ is at the core of flexible human behaviours,” explained Kourtzi. “It underpins how children acquire literacy and numeracy, and how adults develop work-related skills later in life.”

One of the important determinants her team has discovered is that being able to multi-task is better than being able to memorise.

“ ̽��ֱ��faster learners are those who can attend to multiple things at the same time and recruit areas of the brain that are involved in attention,” she explained. “Those who are slower at learning try to memorise, as we can see from greater activity in the parts of the brain connected with memory.”

“So, in fact, being able to do the sort of multi-tasking required when interacting in busy environments or playing video games – which requires the processing of multiple streams of information – can improve your ability to learn.”

She also finds that age doesn’t matter: “what seems to matter is your strategy in life – so if older people have really good attentive abilities they can learn as fast as younger people.”

This has important implications for an ageing society. In the UK, there are now more people over State Pension age than there are children. ̽��ֱ��UK’s Office for National Statistics predicts that, by 2020, people over 50 will make up almost a third of the workforce and almost half of the adult population. ̽��ֱ��average life expectancy for a man in the UK will have risen from 65 years in 1951 to 91 years by 2050. Older age has become an increasingly active phase of people’s lives, one in which re-training and cognitive resilience is increasingly sought after.

Kourtzi and colleagues are using functional magnetic resonance imaging to detect when areas of the brain are activated in response to a sensory input and how these circuits change with learning and experience. While at the ̽��ֱ�� of Birmingham, she showed that the visual recognition abilities of young and older adults can be enhanced by training, but that the different age groups use different neural circuits to do this.

Young adults use anterior brain centres that are often used in perceptual decisions, where sensory information is evaluated for a decision to be made; older adults, by contrast, use the posterior part of the brain, which is in charge of the ability to attend and select a target from irrelevant clutter. “ ̽��ֱ��clear implication of this is that training programmes need to be geared for age,” said Kourtzi.

Crucially, what she also observed is that some people benefit from training more than others: “although it’s well known that practice makes perfect, some people are better at learning and may benefit more from particular interventions than others. But to determine how and why, we need to go beyond biological factors, like cognition or genetics, to look at social factors: what is it about the way a particular individual has learned to approach learning in their social setting that might affect their ability to learn?”

This multidisciplinary approach to understanding learning lies at the heart of her work. She leads the European-Union-funded Adaptive Brain Computations project, which brings together behavioural scientists, computer scientists, pharmacologists and neuroscientists across eight European universities, plus industrial partners, to understand and test how learning happens.

“In our work, there’s a strong element of translating our findings into practical applications, so creating training programmes that are age appropriate is our ultimate goal,” she added.

“ ̽��ֱ��reason we like the Café Wall Illusion so much is because tricks of visual perception tell us that the brain can see things in a different way to the input. How the brain does this is influenced by context, just as the way we interpret our environment is influenced by learning and previous experience.”

Inset image: Café Wall Illusion, Tony Kerr on Flickr

Our brains are plastic. They continually remould neural connections as we learn, experience and adapt. Now researchers are asking if new understanding of these processes can help us train our brains.

In the Café Wall Illusion, the brain takes into account the surrounding tiles, but it also relies on our previous knowledge acquired through training and experience when interpreting a new situation

Zoe Kourtzi

Sam Webster

11 Thinking about it

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From Mexican wave to retinal wave: why sharing data is good for science

jfp40 — Mon, 07 Apr 2014 10:40:34 +0000

Now, researchers at Cambridge, York, Newcastle and Imperial College London have developed a system allowing neurophysiologists to share raw data with each other, something they hope will generate new discoveries in the field. ̽��ֱ��results are published in the journal GigaScience.

̽��ֱ��first type of data they collected and standardised are recordings of so called ‘retinal waves’. During early development, retinal neurons generate signals that rapidly spread across from one cell to another, much like a Mexican wave in a football stadium. These patterns of activity are thought to help forge the neural connections from the eye to the brain.

To record retinal waves, scientists use multielectrode arrays (tiny electrical devices). In this research, the team took 366 recordings from 12 different studies published between 1993 and 2014, converted them all to HDF5 – a standard open source format – and published them in a web-based ‘virtual laboratory’ called CARMEN.

According to lead author Dr Stephen Eglen from the Cambridge Computational Biology Institute: “Unlike other fields such as genomics, there hasn’t been much public data sharing in neuroscience, which could be because the data are heterogeneous and hard to annotate, or because researchers are reluctant to share data with a competitor.”

But Eglen believes there is much to be gained by a more cooperative approach. “There are two main benefits to sharing,” he said. “As well as leading to other collaborations and more interesting research, it also means that other people can check what you’ve done, which leads to more robust research. And if the taxpayer funds research, then I think it’s important for those results to be publicly available.”

CARMEN was a pilot project funded by the EPSRC, and is now supported by the BBSRC.

From the way we learn, to how our memories are made and stored, the workings of our brains depend on connections forged between billions of neurons, yet much about how our nervous system develops remains a mystery.

There are two main benefits to sharing. As well as leading to other collaborations and more interesting research, it also means that other people can check what you’ve done, which leads to more robust research.

Dr Stephen Eglen

Oyvind Solstad

Eye 9

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Windows to the self?

tdk25 — Mon, 29 Oct 2012 16:55:05 +0000

Young children often make the mistake of thinking that you can’t see them if they can’t see you – hiding themselves by covering or closing their eyes. Using a process of elimination, a research team at the ̽��ֱ�� of Cambridge has now found out why.

Testing children aged three and four, the team, led by Dr James Russell from the Department of Psychology, first asked them whether they could be seen if they were wearing a blindfold, and whether the researcher could see an adult who was wearing one. Nearly all the children felt that when they were wearing a mask they were hidden, and most thought the adult wearing a mask was hidden too.

Next, the researchers tested whether children think it is the fact that a person’s eyes are hidden from other people’s view that renders them invisible, or if they think the act of being blinded is the decisive factor.

To test this, a new group of young children were quizzed about their ability to be seen when they were wearing goggles that were completely blacked out, meaning that they could not see and their eyes were hidden. They were then asked about the same issues when wearing a second pair of goggles which were covered in mirrored film – meaning that they could see, but other people could not see their eyes.

Unfortunately, this test did not go quite according to plan. Out of the 37 children involved, only seven were able to grasp the concept that they could see out, but people couldn’t see them. Of these seven, six believed that they were invisible regardless of the goggles that they were wearing. In other words, the children's feelings of invisibility seem to come from the fact that their eyes are hidden, rather than from the fact that they can't see.

In both studies, when the children thought that they were invisible because of their eyes being covered, they nonetheless agreed that their head and body were visible. ̽��ֱ��researchers argue that this represents a distinction in the child’s mind between the concealment of the “self” and that of the body.

Coupled with the fact that hiding their eyes appeared to be the decisive factor when trying to make themselves feel hidden, the researchers wondered if their invisibility beliefs were based around the idea that there must be eye contact between two people – a meeting of gazes – for them to see their “selves”.

This idea appeared to receive some support from a further study in which more children were asked if they could be seen when a researcher looked directly at them while they averted their gaze; or, contrarily, if the researcher with gaze averted was visible while the child looked directly at them.

Many of the children felt that they were hidden so long as they didn’t meet the gaze of the researcher. They also felt that the researcher was hidden if his or her gaze was averted while the child looked on.

“It seems that children apply the principle of joint attention to the self and assume that for somebody to be perceived, experience must be shared and mutually known to be shared, as it is when two pairs of eyes meet,” Russell said.

Other explanations were ruled out with some puppet studies. For instance, the majority of a new group of children agreed it was reasonable for a puppet to hide by covering its eyes, which rules out the argument that children only hide this way because they are caught up in the heat of the moment.

̽��ֱ��revelation that most young children think people can only see each other when their eyes meet raises some interesting questions for future research. For example, children with autism are known to engage in less sharing of attention with other people (following another person's gaze), so perhaps they will be less concerned with the role of mutual gaze in working out who is visible. Another interesting avenue could be to explore the invisibility beliefs of children born blind. ̽��ֱ��authors speculate that skin-to-skin touching may serve as a proxy for eye-contact in the congenitally blind.

Researchers have offered a convincing new theory which explains why children believe that they are invisible when they cover their eyes.

It seems that children apply the principle of joint attention to the self and assume that for somebody to be perceived, experience must be shared and mutually known to be shared, as it is when two pairs of eyes meet

Dr James Russell

Audi insperation from Flickr.

Alice eyes. Researchers found that most children believe that people can only see each other when their eyes meet.

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Surprising solution to fly eye mystery

gm349 — Thu, 11 Oct 2012 19:00:27 +0000

Fly eyes have the fastest visual responses in the animal kingdom, but how they achieve this has long been an enigma. A new study shows that their rapid vision may be a result of their photoreceptors - specialised cells found in the retina - physically contracting in response to light. ̽��ֱ��mechanical force then generates electrical responses that are sent to the brain much faster than, for example, in our own eyes, where responses are generated using traditional chemical messengers. ̽��ֱ��study was published today, in the journal Science.

It had been thought that the ion channels responsible for generating the photoreceptors’ electrical response were activated by chemical messengers as is usually the case in cell signalling pathways. However, these results suggest that the light-sensitive ion channels responsible for the photoreceptor’s electrical response may be physically activated by the contractions – a surprising solution to the mystery of light perception in the fly’s eye and a new concept in cellular signalling.

Professor Roger Hardie, lead author of the study from the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience, said: “ ̽��ֱ��ion channel in question is the so-called ‘transient receptor potential’ (TRP) channel, which we originally identified as the light-sensitive channel in the fly in the 1990’s. It is now recognised as the founding member of one of the largest ion channel families in the genome, with closely related channels playing vital roles throughout our own bodies. As such, TRP channels are increasingly regarded as potential therapeutic targets for numerous pathological conditions, including pain, hypertension, cardiac and pulmonary disease, cancer, rheumatoid arthritis, and cerebral ischaemia. We are therefore hopeful that these new results may have significance well beyond the humble eye of the fly.”

A fly’s vision is so fast that it is capable of tracking movements up to five times faster than our own eyes. This performance is achieved using microvillar photoreceptor cells, in which the photo-receptive membrane is made up of tiny tubular membranous protrusions known as microvilli. In each photoreceptor cell, tens of thousands of these are packed together to form a long rod-like structure, which acts as a light-guide to absorb the incident light. Each microvillus also houses the biochemical machinery, which converts the energy of the absorbed light into the electrical responses that are sent to the brain – a process known as phototransduction.

As in all photoreceptors, phototransduction starts with absorption of light by a visual pigment molecule (rhodopsin). In microvillar photoreceptors this leads to activation of a specific enzyme known as phospholipase C (PLC). PLC is a ubiquitous and very well-studied enzyme, which cleaves a large piece from a specific lipid component of the cell membrane (“PIP₂”), leaving a smaller membrane lipid (DAG) in its place.

Somehow this enzymatic reaction leads to the opening of “ion channels” in the microvillus membrane; once opened, these allow positively charged ions such as Ca²⁺ and Na⁺ to flow into the cell thus generating the electrical response. This basic sequence of events has been established for over 20 years; but exactly how PLC’s enzymatic activity causes the opening of the channels has long remained a mystery and one of the major outstanding questions in sensory biology.

Professor Hardie added: “ ̽��ֱ��conventional wisdom would be that one of the products of this enzyme’s activity is a chemical ‘second messenger’ that binds to and activates the channel. However, years of research had previously failed to find compelling evidence for such a straightforward mechanism.”

̽��ֱ��new study, which was funded by the BBSRC and the Medical Research Council, using the fruitfly, Drosophila, now suggests a remarkable and unexpected resolution to this mystery. ̽��ֱ��key finding was that the photoreceptors physically contract in response to light flashes. ̽��ֱ��contractions were so small and fast that an “atomic force microscope” was needed to measure them. This revealed that the contractions were even faster than the cell’s electrical response and appeared to be caused directly by PLC activity.

̽��ֱ��researchers believe that the splitting of the membrane lipid PIP₂ by the enzyme PLC reduces the membrane area, thereby increasing tension in the membrane and causing each tiny microvillus to contract in response to light. ̽��ֱ��synchronised contraction of thousands of microvilli together then accounts for the contractions measured from the whole cell.

Dr Kristian Franze, co-author of the paper from the ̽��ֱ�� of Cambridge, said: “We propose that within each microvillus the increase in membrane tension acts directly on the light-sensitive channels. In other words, rather than using a traditional chemical 2^nd messenger, the channels were being activated mechanically.”

This concept was supported by experiments in which the native light-sensitive channels were eliminated by mutation and replaced with mechano-sensitive channels, which are known to open in response to membrane tension. Remarkably, these photoreceptors still generated electrical signals in response to light, but were now mediated by activation of the ectopic mechano-sensitive channels. To test whether the native light-sensitive channels could be affected by mechanical forces in the membrane, the microvillar membrane was stretched or compressed by changing the osmotic pressure. This simple experimental manipulation rapidly enhanced or suppressed channel openings in response to light as predicted.

These results suggest that PLC mediates its effects in the photoreceptors by changing the mechanical state of the membrane. ̽��ֱ��researchers suggest that it is the increase in the membrane tension (along with a pH change also resulting from PLC activity) that triggers the opening of the light-sensitive channels. Mechano-sensitive ion channels are actually well known, but normally involved in transducing mechanical stimuli – such as sound in the ears or pressure on the skin. One of their characteristics is that they can be activated extremely rapidly – perhaps an explanation for why fly photoreceptors have evolved this solution to phototransduction.

Professor Hardie said: “That a mechanical signal could be an intermediate signal -or ‘second messenger’- in an otherwise purely biochemical cascade is a novel concept that extends our understanding of cellular signalling mechanisms to a new level.”

For more information, please contact Genevieve Maul (genevieve.maul@admin.cam.ac.uk) at the ̽��ֱ�� of Cambridge Office of External Affairs and Communications.

Research provides insight into why flies have the fastest vision in the animal kingdom.

̽��ֱ��conventional wisdom would be that one of the products of this enzyme’s activity is a chemical ‘second messenger’ that binds to and activates the channel. However, years of research had previously failed to find compelling evidence for such a straightforward mechanism.

Professor Roger Hardie, lead author of the study from the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience

Image H. Meinecke

Blowfly

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Researchers develop new test for children with vision loss

sjr81 — Tue, 11 Oct 2011 15:47:27 +0000

Dr Louise Allen, a paediatric ophthalmologist at the ̽��ֱ�� of Cambridge, and Dr Adar Pelah, an electronics engineer at the ̽��ֱ�� of York, have developed a specialised visual field test system to detect peripheral vision defects, called KidzEyez.

Peripheral visual field loss in children can result from prematurity, eye disorders such as retinal dystrophy, brain conditions such as cerebral palsy, neurosurgery, drug therapy, or brain tumours.

Most children with brain tumours will develop visual field loss due to the tumour’s interference with the visual pathway, which stretches from the optic nerve at the very front of the brain to the visual cortex at the back of the brain. Unfortunately, visual field loss in young children is currently very difficult to assess; timely recognition could lead to earlier diagnosis and treatment of its cause, resulting in the prevention of severe visual impairment, improved outcomes and more individualised support.

Current techniques for measuring the peripheral visual field require the subject to sit still and maintain a steady gaze at a light target for as long as ten minutes. These tests can be difficult enough for an adult to perform, let alone a young child.

̽��ֱ��clinical need for a perimeter suitable for use in young children led Dr Allen and Dr Pelah to develop a system which is child-friendly, fast, but accurate in detecting peripheral visual field loss.

Using the KidzEyez system, the child watches a central cartoon on a video screen, while their natural looking response to a target appearing in different locations of the visual periphery is monitored remotely using a small camera located on the video screen. If the target falls within the intact visual field, the child will reflexively look at the target; if the target falls within a blind area, no response will be seen.

“KidzEyez is the first perimeter specifically designed for young children,” said Dr Allen. “Children find the testing fun and, by improving our detection and management of visual pathway tumours, KidzEyez could play a major role in preserving sight and improving our support of children with visual impairment.”

A trial of the KidzEyez perimeter at Addenbrooke’s Hospital, Cambridge has recently been completed on 74 children between three and 10 years of age, some with and some without predicted visual field loss. ̽��ֱ��results were compared with currently available confrontation testing, which involves the examination of the child’s response to a small toy held in their visual periphery. KidzEyez was found to have 100% sensitivity and specificity compared to confrontation testing but, importantly, gave an interpretable result in more than 70% of children whose concentration was too poor for confrontation testing.

Dr Allen will present the findings of the study at the conference of the British Isles Paediatric Ophthalmology and Strabismus Association this week in London.

KidzEyez has been funded by Cambridge Enterprise, the ̽��ֱ��’s commercialisation group, and the ̽��ֱ�� of York. Cambridge Enterprise is currently seeking commercial partners for licensing, collaboration and development of this technology.

Technology developed at the ̽��ֱ�� of Cambridge to detect peripheral visual field loss in young children will enable the earlier detection of brain tumours, potentially saving sight and lives.

KidzEyez is the first perimeter specifically designed for young children.

Louise Allen

Cambridge Enterprise

Dr Louise Allen

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Rebellion, repression, retribution

tdk25 — Fri, 01 Feb 2008 00:00:00 +0000

̽��ֱ��true course of events of the Irish rebellion of 1641 has never been fully known. Initiated by disaffected Irish Catholics rebelling against Protestant settlers, the rebellion quickly escalated in violence, resulting in widespread killing. But was the rebellion intended to be a bloodless coup that spiralled out of control, or were the thousands of Protestants deliberately driven out and massacred? What’s clear is that the years that followed were a time of savage revenge for the events of 1641 – Oliver Cromwell arrived with 30,000 English troops to conquer Ireland in the name of the English Republic and to exact ‘a just judgement of God upon those barbarous wretches, who have imbrued their hands in so much innocent blood’ – and the groundwork was laid for Ireland’s Catholic–Protestant divide.

A curious aspect of the rebellion is that although it is the least understood of all the great massacres of European history, it is amongst the best recorded. Historical narratives in the form of eyewitness accounts of those who lived through the rebellion are still in existence in the library of Trinity College Dublin, where they have remained largely unstudied. This is chiefly because there is too much of a record of what happened and it has taken until now, with improvements in technology and the political climate, to conspire finally to make it possible for the secrets of the ‘1641 depositions’ to be unlocked. A team of scholars in Cambridge, Dublin and Aberdeen are poised to do just this. Professor John Morrill from Cambridge’s Faculty of History is chairing the three-year project, working alongside Professor Jane Ohlmeyer and Dr Micheál Ó Siochrú (Trinity College Dublin), and Professor Tom Bartlett ( ̽��ֱ�� of Aberdeen).

Roots of an uprising

̽��ֱ��1641 rebellion had roots stretching back to the mid-16th century, when the Irish provinces were heavily colonised by English settlers. Throughout the reign of Queen Elizabeth I, the English government, fearful that continental Catholic kings would use Ireland as a springboard for invading England to exploit the dynastic weaknesses (Elizabeth was, in Catholic eyes, a heretic bastard tyrant, unmarried and the last of her line), sought to impose strong Protestant control of Ireland. This led to a dreadful cycle: Catholic rebellion, repression of the uprising, replacement of Irish landowners by English as part of a ‘Plantation’ policy, then more rebellion, more repression and further Plantation.

In and after 1610, the largest of the Plantation policies, in which not only the Irish landowners but also the tenant farmers and urban elites were displaced, affected large parts of Ulster in the far north of Ireland. Previous Catholic owners and occupiers were driven into exile, where thousands either became mercenary soldiers (‘Wild Geese’) in the armies of the Habsburg kings or fell into destitution.

For 30 years, the strong authoritarian government, softened by a blind-eye to private Catholic worship, kept the dispossessed of Ulster and elsewhere in check. But in 1641, England was paralysed by the disputes that were to lead, a year later, to civil war.

King Charles I’s puritan opponents had plans to introduce much more effective religious persecution of the Catholic Irish and to make Ireland increasingly part of an enlarged English state. This provoked, from late October 1641, a series of pre-emptive strikes by members of the Catholic nobility and, in the ensuing chaos, a series of what (unless this research project tells otherwise) appear to be spontaneous revenge attacks on Protestant settlers that quickly got out of control.

An imperfect account

Although we have no idea how many people were killed during the events of 1641, the most prudent estimates are that 4000 died through acts of violence and that 6000 more died of the consequences of being driven out naked into the winter cold, while many more fled from their homes and made their way eventually back to England. So much is clear. But the precise chronology and geography of the rebellion have remained hazy at best.

̽��ֱ��English government had to do something to protect the English Protestant settlers, but their own country was in chaos. They could not raise taxes to fund the army. So they borrowed money from 2000 venture capitalists (the ‘Adventurers’) against the promise that they would receive two million acres of Irish land once Ireland was conquered. To establish which land was to be confiscated, all (mainly Protestant) witnesses to the rebellion were questioned by government-appointed commissioners and their accounts recorded as ‘depositions’ that could be used in court.

Today, 3400 depositions are in existence, providing the fullest and most dramatic evidence we have for any event of this kind before the 20th century. They add to up 19,000 pages of testimony in crabbed 17th-century hands. Trinity College Library acquired the documents in 1741 and for centuries there they have remained, far too extensive for any one scholar to explore them all and in too poor a condition for widespread access. Even with a team of researchers, it will take a total of more than eight person years to transcribe the accounts.

A new kind of history

̽��ֱ��spirit of co-operation between the UK and Irish governments following the Good Friday agreement has made it possible to fund a project of this size – the most ambitious British-Irish collaboration in the humanities ever undertaken. Separate but linked funding streams in the UK and Ireland have raised more than 1 million euros from the Arts and Humanities Research Council (AHRC) in the UK, the Irish Research Council for the Humanities and Social Sciences (IRCHSS) and Trinity College Dublin.

Once the depositions are captured and online, they will constitute a database that can be arranged and re-arranged in any way a scholar would like: by date, by map reference, even by act of violence. Many of the depositions give detailed inventories of goods taken and destroyed, affording unique insights into the material culture of a colonial society. Members of the general public might even use depositions to trace family trees. There are endless possibilities for further study, both looking backwards to the pattern of exploitation that provoked the explosion of Catholic violence, and forwards to the way in which these massacres resulted in the confiscation of 40% of the land of Ireland and its transfer from Catholics born in Ireland to Protestants born in England. These are events that transformed Irish history and therefore British and world history. This collaborative project represents a new kind of history: one where the medium and the message can change how we understand ourselves in time.

For more information, please contact the author Professor John Morrill (jsm1000@cam.ac.uk) at the Faculty of History.

John Morrill explores one of the most extraordinary and least understood aspects of Anglo-Irish history - the rebellion of 1641.

But was the rebellion intended to be a bloodless coup that spiralled out of control, or were the thousands of Protestants deliberately driven out and massacred?

Credit- the Board of Trinity College, Dublin

Deposition taken from a witness to the 1641 Irish rebellion

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