Fish eyes may hold key to blindness cure: study

March 11, 2017

Washington, Mar 11: Scientists, including one of Indian-origin, have identified a chemical signal in the zebrafish brain that helps it regenerate retina, a finding that may help cure blindness in humans.

fisheye

The discovery raises the possibility that human retinas can be induced to regenerate, naturally repairing damage caused by degenerative retinal diseases and injury, including age-related macular degeneration and retinitis pigmentosa, researchers said.

"The prevailing belief has been that the regeneration process in fish retinas is triggered by secreted growth factors, but our results indicate that the neurotransmitter GABA might initiate the process instead," said James Patton, Professor at Vanderbilt University in the US.

"All the regeneration models assume that a retina must be seriously damaged before regeneration takes place, but our studies indicate that GABA can induce this process even in undamaged retinas," said Patton.

It turns out that the structure of the retinas of fish and mammals are basically the same.

Although the retina is very thin - less than 0.5 millimetres thick - it contains three layers of nerve cells: photoreceptors that detect the light, horizontal cells that integrate the signals from the photoreceptors and ganglion cells that receive the visual information and route it to the brain.

In addition, the retina contains a special type of adult stem cell, called Muller glia, that span all three layers and provide mechanical support and electrical insulation. In fish retinas, they also play a key role in regeneration.

When regeneration is triggered, the Muller glia dedifferentiate, begin proliferating, and then differentiate into replacements for the damaged nerve cells. Muller glia are also present in mammalian retinas, but do not regenerate.

Graduate student Mahesh Rao got the idea that GABA - normally a fast-acting neurotransmitter best known for its role of calming nervous activity by inhibiting nerve transmission in the brain - might be the trigger for retinal regeneration.

He was inspired by the results of a study in the mouse hippocampus which found that GABA was controlling stem cell activity.

Working with Patton and assistant professor Dominic Didiano, Rao designed a series of experiments with zebrafish which determined that high concentrations of GABA in the retina keep the Miller glia quiescent and that they begin dedifferentiating and proliferating when GABA concentrations drop.

They tested their hypothesis in two ways: By blinding zebrafish and injecting them with drugs that stimulate GABA production and by injecting normal zebrafish with an enzyme that lowers the GABA levels in their eyes.

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June 11,2020

The World Health Organisation (WHO) Director-General Tedros Adhanom Ghebreyesus said that more research needs to be done to better understand the extent to which COVID-19 is being spread by people who don't show symptoms.

"Since early February, we have said that asymptomatic people can transmit COVID-19, but that we need more research to establish the extent of asymptomatic transmission," the WHO chief said at a virtual press conference from Geneva on Wednesday, Xinhua news agency reported.

"That research is ongoing, and we're seeing more and more research being done," he added.

Saying that the world has been achieving a lot in knowing the new virus, the WHO chief told reporters that "there's still a lot we don't

"WHO's advice will continue to evolve as new information becomes available," he said.

Tedros stressed that the most critical way to stop transmission is to find, isolate and test people with symptoms, and trace and quarantine their contacts.

"Many countries have succeeded in suppressing transmission and controlling the virus doing exactly this," Tedros said.

Meanwhile, Michael Ryan, executive director of WHO Health Emergencies Program, said Wednesday that the COVID-19 pandemic is still evolving.

"If we look at the numbers... this pandemic is still evolving. It is growing in many parts of the world," he said. "We have deep concerns that health systems of some countries are struggling, under a huge strain and require our support, our help and our solidarity."

He said "each and every country has a different combination of risks and opportunities, and it's really down to national authorities to carefully consider where they are in the pandemic."

In Europe, the risk issue now are about travels and the opening of the schools, around risk management, mass gathering, surveillance and contact tracing, said the WHO official.

In Southeast Asian countries, where to a great extent transmissions have been under control, governments are more concerned about the re-emergence of clusters, while in South America, the issue of PPE for health workers has not gone away, said Ryan.

As regards Africa, Ryan said the death rates have been very low in the past week, but the health system can be overwhelmed, as it would have to cope with other diseases such as malaria.

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June 10,2020

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.

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June 22,2020

A team of scientists has produced first open source all-atom models of full-length COVID-19 Spike protein that facilitates viral entry into host cells – a discovery that can facilitate a faster vaccine and antiviral drug development.

The group from Seoul National University in South Korea, University of Cambridge in the UK and Lehigh University in the US produced the first open-source all-atom models of a full-length S protein.

The researchers say this is of particular importance because the S protein plays a central role in viral entry into cells, making it a main target for vaccine and antiviral drug development.

"Our models are the first full-length SARS-CoV-2 spike (S) protein models that are available to other scientists," said Wonpil Im, a professor in Lehigh University.

"Our team spent days and nights to build these models very carefully from the known cryo-EM structure portions. Modeling was very challenging because there were many regions where simple modeling failed to provide high-quality models," he wrote in a paper published in The Journal of Physical Chemistry B.

Scientists can use the models to conduct innovative and novel simulation research for the prevention and treatment of Covid-19.

Though the coronavirus uses many different proteins to replicate and invade cells, the Spike protein is the major surface protein that it uses to bind to a receptor.

The total number of global COVID-19 cases was nearing 9 million, while the deaths have increased to over 467,000, according to the Johns Hopkins University.

With 2,279,306 cases and 119,967 deaths, the US continues with the world's highest number of COVID-19 infections and fatalities, according to the CSSE.

Brazil comes in the second place with 1,083,341 infections and 50,591 deaths.

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