Posts tagged photoreceptors
Articles and news from the latest research reports.
Study of how eye cells become damaged could help prevent blindness
Light-sensing cells in the eye rely on their outer segment to convert light into neural signals that allow us to see. But because of its unique cylindrical shape, the outer segment is prone to breakage, which can cause blindness in humans. A study published by Cell Press on January 22nd in the Biophysical Journal provides new insight into the mechanical properties that cause the outer segment to snap under pressure. The new experimental and theoretical findings help to explain the origin of severe eye diseases and could lead to new ways of preventing blindness.
"To our knowledge, this is the first theory that explains how the structural rigidity of the outer segment can make it prone to damage," says senior study author Aphrodite Ahmadi of the State University of New York Cortland. "Our theory represents a significant advance in our understanding of retinal degenerative diseases."
The outer segment of photoreceptors consists of discs packed with a light-sensitive protein called rhodopsin. Discs made at nighttime are different from those produced during the day, generating a banding pattern that was first observed in frogs but is common across species. Mutations that affect photoreceptors often destabilize the outer segment and may damage its discs, leading to cell death, retinal degeneration, and blindness in humans. But until now, it was unclear which structural properties of the outer segment determine its susceptibility to damage.
To address this question, Ahmadi and her team examined tadpole photoreceptors under the microscope while subjecting them to fluid forces. They found that high-density bands packed with a high concentration of rhodopsin were very rigid, which made them more susceptible to breakage than low-density bands consisting of less rhodopsin. Their model confirmed their experimental results and revealed factors that determine the critical force needed to break the outer segment.
The findings support the idea that mutations causing rhodopsin to aggregate can destabilize the outer segment, eventually causing blindness. “Further refinement of the model could lead to novel ways to stabilize the outer segment and could delay the onset of blindness,” says Ahmadi.
Specific protein essential for healthy eyes
Researchers at the Hebrew University of Jerusalem, in collaboration with researchers at the Salk Institute in California, have found for the first time that a specific protein is essential not only for maintaining a healthy retina in the eye, but also may have implications for understanding and possibly treating other conditions in the immune, reproductive, vascular and nervous systems, as well as in various cancers.
Their work, reported online in the journal Neuron, highlights the role of Protein S in the maintenance of a healthy retina through its involvement in the process of pruning photoreceptors, the light-sensitive neurons in the eye. (This process is also referred to as phagocytosis.) These photoreceptors keep growing and elongating from their inner end. In order to maintain a constant length, they must be pruned from their outer end by specialized cells called retinal pigment epithelial cells.
Without such pruning — which also clears away many free radicals and toxic by-products generated during visual biochemical reactions — photoreceptors would succumb to toxicity and degenerate, leading if unchecked to blindness. A receptor molecule called Mer is a key in photoreceptor pruning, and is therefore vital for retinal health. Mutations in the mouse, rat and human Mer genes cause retinal degeneration, which finally leads to blindness.
The Hebrew University study published in Neuron focuses on the molecules activating Mer in this pruning mechanism. Although two such molecules – Gas6 and Protein S — were identified previously, it was yet to be proven that they also play a role in a living organism. To show this, Dr. Tal Burstyn-Cohen of the Hebrew University Institute of Dental Sciences and colleagues at the Salk Institute in California found in their experiments on laboratory animals that both Gas6 and Protein S are needed to activate phagocytosis, or pruning, of retinal photoreceptors, and thus keep a healthy retina.
These findings could have practical implications, since Protein S also functions as a potent blood anticoagulant. People with Protein S deficiency are at risk for life threatening thrombosis (blood clots) and thromboembolism (a clot that breaks loose and is carried by the blood stream to plug another vessel).
These results further open new avenues of research into the role of Protein S in activating the receptors in other tissues where their function was shown to be important, such as in the immune, reproductive, vascular and nervous systems, as well as in various cancers where activation of receptors has been observed. For example, since Protein S is important for blood vessel formation, neutralizing Protein S in the blood vessels supplying blood to cancer growths could interfere with the cancerous blood supply.
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Totally blind mice get sight back
Totally blind mice have had their sight restored by injections of light-sensing cells into the eye, UK researchers report. The team in Oxford said their studies closely resemble the treatments that would be needed in people with degenerative eye disease. Similar results have already been achieved with night-blind mice.
Experts said the field was advancing rapidly, but there were still questions about the quality of vision restored. Patients with retinitis pigmentosa gradually lose light-sensing cells from the retina and can become blind. The research team, at the University of Oxford, used mice with a complete lack of light-sensing photoreceptor cells in their retinas. The mice were unable to tell the difference between light and dark.
Reconstruction
They injected “precursor” cells which will develop into the building blocks of a retina once inside the eye. Two weeks after the injections a retina had formed, according to the findings presented in the Proceedings of the National Academy of Sciences journal. Prof Robert MacLaren said: “We have recreated the whole structure, basically it’s the first proof that you can take a completely blind mouse, put the cells in and reconstruct the entire light-sensitive layer.”
Previous studies have achieved similar results with mice that had a partially degenerated retina. Prof MacLaren said this was like “restoring a whole computer screen rather than repairing individual pixels”. The mice were tested to see if they fled being in a bright area, if their pupils constricted in response to light and had their brain scanned to see if visual information was being processed by the mind.
Vision
Prof Pete Coffee, from the Institute of Ophthalmology at University College London, said the findings were important as they looked at the “most clinically relevant and severe case” of blindness. “This is probably what you would need to do to restore sight in a patient that has lost their vision,” he said.
However, he said this and similar studies needed to show how good the recovered vision was as brain scans and tests of light sensitivity were not enough. He said: “Can they tell the difference between a nasty animal and something to eat?”
Prof Robin Ali published research in the journal Nature showing that transplanting cells could restore vision in night-blind mice and then showed the same technique worked in a range of mice with degenerated retinas. He said: “These papers demonstrate that it is possible to transplant photoreceptor cells into a range of mice even with a severe level of degeneration. “I think it’s great that another group is showing the utility of photoreceptor transplantation.”
Researchers are already trialling human embryonic stem cells, at Moorfields Eye Hospital, in patients with Stargardt’s disease. Early results suggest the technique is safe but reliable results will take several years.
Retinal chips or bionic eyes are also being trailed in patients with retinitis pigmentosa.
Light on the Brain
By Sabrina Richards | September 20, 2012
Researchers find that photoreceptors expressed in zebrafish hypothalamus contribute to light-dependent behavior.
Juvenile zebrafish.
Zebrafish larvae without eyes or pineal glands can still respond to light using photopigments located deep within their brains. Published in Current Biology, the findings are the first to link opsins, photoreceptors located in the hypothalamus and other brain areas, to increased swimming in response to darkness, a behavior researchers hypothesize may help the fish move toward better-lit environments.
“[It’s a] strong demonstration that opsin-dependent photoreceptors in deep brain areas affect behaviors,” said Samer Hattar, who studies light reception in mammals at Johns Hopkins University but did not participate in the research.
Photoreceptors in eyes enable vision, and photoreceptors in the pineal gland, a small endocrine gland located in the center of the vertebrate brain, regulate circadian rhythms. But photoreceptors are also found in other brain areas of both invertebrates and vertebrate lineages. The function of these extraocular photoreceptors has been best studied in birds, where they regulate seasonal reproduction, explained Harold Burgess, a behavioral neurogeneticist at the Eunice Kennedy Shriver National Institute for Child Health and Human Development.
Many opsins have been reported in the brains of tiny and transparent larval zebrafish, raising the possibility that light could be stimulating the photoreceptors even deep in the brain. To test for behaviors that may be regulated by deep brain photoreceptors, Burgess and his colleagues in Wolfgang Driever’s lab at the University of Freiburg removed the eyes of zebrafish larvae, and compared their behavior to larvae that retained their eyes. Although most light-dependent behavior required eyes, the eyeless larvae did respond when the lights were turned off, increasing their activity for a several minutes, though to a somewhat lesser extent than control larvae. But the fact that they responded at all suggests that non-retinal photoreceptors contributed to the behavior.
To confirm the role of the deep brain photoreceptors, the researchers also tested eyeless larvae that had been genetically modified to block expression of photoreceptors in the pineal gland. This fish still showed this jump in activity for several minutes after entering darkness.
Two different types of opsins—melanopsin and multiple tissue opsin—are expressed in the same type of neuron in zebrafish hypothalamus. Burgess and his colleagues looked at zebrafish missing the transcription factor Orthopedia, which is unique to these neurons, and found that the darkness-induced activity boost is nearly absent in these fish. To further narrow the search for the responsible photoreceptors, the researchers overexpressed melanopsin in hypothalamus neurons that co-express Orthopedia and melanopsin, and found that it increased the sensitivity of eyeless zebrafish to reductions in light. The results point to both melanopsin and Orthopedia as key players in modulating this behavior and pinpoint the location to neurons that coexpress these factors in the zebrafish hypothalamus.
Interestingly, the hypothalamus is one of the oldest parts of the vertebrate brain, said Detlev Arendt, a developmental biologist at the European Molecular Biology Laboratory in Heidelberg. “It’s very possible that this is one of the oldest functions”—one that evolved in “non-visual organisms” that had no eyes but still needed to sense light.
Although not as directed and efficient as eye-dependent behaviors that help fish swim toward light, Burgess speculates that deep brain opsins can still benefit zebrafish larvae. “You could imagine situation where it can’t see light, if a leaf falls on it and it doesn’t know where to swim. I think this behavior puts it in a hyperactive state where it swims wildly for several minutes until it reaches enough light for eyes to take over,” he explained, noting that such behavior is common in invertebrates.
It remains to be seen whether these deep brain opsins regulate other behaviors, perhaps in similar fashion to seasonal hormonal regulation in birds, but Hattar believes it is likely. “It’s beyond reasonable doubt there are many functions for these deep brain photoreceptors.”
(Source: the-scientist.com)