Hours after death, eyes respond to to light + RNA origin of life gets new support

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Life after death for human eye: Vision scientists revive light-sensing cells in organ donor eyes
https://healthcare.utah.edu/moran/news/2...nature.php

RELEASE: Scientists have revived light-sensing neuron cells in organ donor eyes and restored communication between them as part of a series of discoveries that stand to transform brain and vision research. Billions of neurons in the central nervous system transmit sensory information as electrical signals; in the eye, specialized neurons known as photoreceptors sense light.

Publishing in Nature, a team of researchers from the John A. Moran Eye Center at the University of Utah and Scripps Research collaborators describe how they used the retina as a model of the central nervous system to investigate how neurons die -- and new methods to revive them.

"We were able to wake up photoreceptor cells in the human macula, which is the part of the retina responsible for our central vision and our ability to see fine detail and color," explains Moran Eye Center scientist Fatima Abbas, PhD, lead author of the published study. "In eyes obtained up to five hours after an organ donor's death, these cells responded to bright light, colored lights, and even very dim flashes of light."

While initial experiments revived the photoreceptors, the cells appeared to have lost their ability to communicate with other cells in the retina. The team identified oxygen deprivation as the critical factor leading to this loss of communication.

To overcome the challenge, Scripps Research Associate Professor Anne Hanneken, MD, procured organ donor eyes in under 20 minutes from the time of death, while Moran Eye Center scientist Frans Vinberg, PhD, designed a special transportation unit to restore oxygenation and other nutrients to the organ donor eyes.

Vinberg also built a device to stimulate the retina and measure the electrical activity of its cells. With this approach, the team was able to restore a specific electrical signal seen in living eyes, the "b wave." It is the first b wave recording made from the central retina of postmortem human eyes.

"We were able to make the retinal cells talk to each other, the way they do in the living eye to mediate human vision," says Vinberg. "Past studies have restored very limited electrical activity in organ donor eyes, but this has never been achieved in the macula, and never to the extent we have now demonstrated."

The process demonstrated by the team could be used to study other neuronal tissues in the central nervous system. It is a transformative technical advance that can help researchers develop a better understanding of neurodegenerative diseases, including blinding retinal diseases such as age-related macular degeneration.

The Nature study, "Revival of light signaling in the postmortem mouse and human retina," has now provided data from over 40 human donor eyes -- including the first description of a mechanism that is expected to rate-limit the speed of human central vision.

Vinberg points out this approach can reduce research costs compared to non-human primate research and dependence on animal models that produce results that do not always apply to humans. While mice are commonly used in vision research, they do not have a macula. Researchers can also test potential new therapies on functioning human eye cells, speeding drug development.

"The scientific community can now study human vision in ways that just aren't possible with laboratory animals," says Vinberg. "We hope this will motivate organ donor societies, organ donors, and eye banks by helping them understand the exciting new possibilities this type of research offers."

Hanneken, who is also a long-time retinal surgeon affiliated with Scripps Memorial Hospital La Jolla, said the ability to produce viable patches of human retinal tissue could lead to new therapies for blinding diseases.

"Until now, it hasn't been possible to get the cells in all of the different layers of the central retina to communicate with each other the way they normally do in a living retina," Hanneken said. "Going forward, we'll be able to use this approach to develop treatments to improve vision and light signaling in eyes with macular diseases, such as age-related macular degeneration."

The Nature study joins a body of science raising questions about the irreversible nature of death, partly defined by the irreversible loss of neuronal activity. Yale University researchers made headlines when they revived the disembodied brains of pigs four hours after death, but they did not restore global neuronal activity.

https://youtu.be/d_5VlMl4bkE

https://www.youtube-nocookie.com/embed/d_5VlMl4bkE


Origin of life theory involving RNA-protein hybrid gets new support
https://www.lmu.de/en/newsroom/news-over...shift.html

RELEASE: According to a new concept by LMU chemists led by Thomas Carell, it was a novel molecular species composed out of RNA and peptides that set in motion the evolution of life into more complex forms

Investigating the question as to how life could emerge long ago on the early Earth is one of the most fascinating challenges for science. Which conditions must have prevailed for the basic building blocks of more complex life to form? One of the main answers is based upon the so-called RNA world idea, which molecular biology pioneer Walter Gilbert formulated in 1986. The hypothesis holds that nucleotides -- the basic building blocks of the nucleic acids A, C, G, and U -- emerged out of the primordial soup, and that short RNA molecules then formed out of the nucleotides. These so-called oligonucleotides were already capable of encoding small amounts of genetic information.

As such single-stranded RNA molecules could also combine into double strands, however, this gave rise to the theoretical possibility that the molecules could replicate themselves -- i.e. reproduce. Only two nucleotides fit together in each case, meaning that one strand is the exact counterpart of another and thus forms the template for another strand.

In the course of evolution, this replication could have improved and at some stage yielded more complex life. "The RNA world idea has the big advantage that it sketches out a pathway whereby complex biomolecules such as nucleic acids with optimized catalytic and, at the same time, information-coding properties can emerge," says LMU chemist Thomas Carell. Genetic material, as we understand it today, is made up of double strands of DNA, a slightly modified, durable form of macromolecule composed of nucleotides.

However, the hypothesis is not without its issues. For example, RNS is a very fragile molecule, especially when it gets longer. Furthermore, it is not clear how the linking of RNA molecules with the world of proteins could have come about, for which the genetic material, as we know, supplies the blueprints. As laid out in a new paper published in Nature, Carell's working group has discovered a way in which this linking could have occurred.

To understand, we must take another, closer look at RNA. In itself, RNA is a complicated macromolecule. In addition to the four canonical bases A, C, G, and U, which encode genetic information, it also contains non-canonical bases, some of which have very unusual structures. These non-information-coding nucleotides are very important for the functioning of RNA molecules. We currently have knowledge of more than 120 such modified RNA nucleosides, which nature incorporates into RNA molecules. It is highly probable that they are relicts of the former RNA world.

The Carell group has now discovered that these non-canonical nucleosides are the key ingredient, as it were, that allows the RNA world to link up with the world of proteins. Some of these molecular fossils can, when located in RNA, "adorn" themselves with individual amino acids or even small chains of them (peptides), according to Carell. This results in small chimeric RNA-peptide structures when amino acids or peptides happen to be present in a solution simultaneously alongside the RNA. In such structures, the amino acids and peptides linked to the RNA then even react with each other to form ever larger and more complex peptides. "In this way, we created RNA-peptide particles in the lab that could encode genetic information and even formed lengthening peptides," says Carell.

The ancient fossil nucleosides are therefore somewhat akin to nuclei in RNA, forming a core upon which long peptide chains can grow. On some strands of RNA, the peptides were even growing at several points. "That was a very surprising discovery," says Carell. "It's possible that there never was a pure RNA world, but that RNA and peptides co-existed from the beginning in a common molecule." As such, we should expand the concept of an RNA world to that of an RNA-peptide world. The peptides and the RNA mutually supported each other in their evolution, the new idea proposes.

According to the new theory, a decisive element at the beginning was the presence of RNA molecules that could adorn themselves with amino acids and peptides and so join them into larger peptide structures. "RNA developed slowly into a constantly improving amino acid linking catalyst," says Carell. This relationship between RNA and peptides or proteins has remained to this day. The most important RNA catalyst is the ribosome, which still links amino acids into long peptide chains today. One of the most complicated RNA machines, it is responsible in every cell for translating genetic information into functional proteins. "The RNA-peptide world thus solves the chicken-and-egg problem," says Carell. "The new idea creates a foundation upon which the origin of life gradually becomes explicable."
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