Unique Schwann cells: the eyes have it

Date:
November 23, 2020
Source:
University of Connecticut
Summary:
Neuroscience researchers are finding genetic properties of Schwann
cells in the cornea that may unlock a better understanding of
their role in healing, sensory function, preserving vision, and
even nerve regeneration.



FULL STORY ==========================================================================
The insulation around nerve cell components in our corneas have unique properties, and little is known about them. But UConn School of Medicine neuroscience professor Royce Mohan believes his lab is on the verge of uncovering a path to better understanding that ultimately could lead to
several vision-preserving advances.


========================================================================== Learning more about the cellular environment in the cornea, including what
are known as glial cells that wrap around the nerve cell's axons, could
have implications for healing after surgeries and corneal transplants,
as well as nerve regeneration, not just in the eyes but potentially in
other systems of the body.

In a paper published in the Journal of Neuroscience Research, lead author
Paola Bargagna-Mohan, assistant professor of neuroscience, details a
method of characterizing every cell in the cornea using an approach
known as single-cell RNA sequence analysis to answer questions about
the cornea's healing process.

The study was done through a collaboration with Paul Robson, associate professor and director of single cell biology at The Jackson Laboratory
for Genomic Medicine (JAX), which houses state-of-the art facilities
for this type of research.

"Going in we knew there would be challenges," says Bargagna-Mohan, a
recipient of a UConn Research Excellence Program award. "After several attempts, we were finally able to optimize our experimental approach to
our advantage. I was extremely excited to get the funding from the UConn
Vice President for Research at this critical time to drive this project."
A material known as myelin insulates axons of nerve fibers and enhances transmission of impulses among neurons. But nature has made the cornea an exception. Myelin in the cornea would interfere with light transmission.

Therefore, the non-myelinating corneal Schwann cells, aptly called so
because they do not produce myelin, are adapted to maintain corneal transparency, optimizing the focus of light on the retina, a crucial
element of our vision.

"This class of glial cells, better known as Schwann cells, have never
before been isolated and characterized," Mohan says. "So this is the
first big step we took to help this field move forward in trying to
repair the nerves of the cornea after surgeries, and also to understand
corneal pain."The Mohan Lab's single-cell RNA sequence analysis enables
access to these cells to study them to an unprecedented extent.



==========================================================================
"All the genes that are expressed in each of the cells can be
characterized," Mohan says. "But not all cells are equal, even within a
certain cell type, cells are never equal. And so cells that are sitting
on the peripheral side of the cornea could be very different from the
cells in the middle of the cornea.

And by characterizing them, we can actually interpret that information to
know what genes are expressed at the corner of the eye versus the one in
the middle of the eye." Mohan, who holds the John A. and Florence Mattern Solomon Endowed Chair in Vision Biology and Eye Research, says this method already has uncovered unique genes that are not expressed in Schwann cells
of other tissues, which may eventually solve the mystery of how corneal
Schwann cells function without interfering with light transmission.

He has a grant application pending with the National Eye Institute to
continue his study of these unique cells and their role in nerve repair
and sensory function.

When it comes to corneal transplants -- relatively common procedures
throughout the world that would be even more common if there were enough
donor corneas available to meet demand -- one of the associated risks
is the recipient doesn't necessarily regain full sensory function of
the eye. The corneal nerves' hypersensitivity to foreign bodies is an evolutionary mechanism of injury prevention.

"If you don't get the sensory function, you may accidentally touch
your eye and injure your cornea, and that could be very traumatic
for someone who's just had a corneal transplant," Mohan says, noting
that donor corneas generally can be preserved for several days. "We
would be very interested to know how the Schwann cells survive in the
existing donor tissue. Is there something we could do to enhance their
survival into even higher levels? And, as well, after the operation is
done?" Sensory function is also a consideration for those who undergo laser-assisted in-situ keratomileusis. Commonly known as LASIK, it's a
vision correction procedure in which the corneal axons are cut and the
Schwann cells are injured.



========================================================================== "They also get some side effects like burning sensation, gritty feeling,
and the exact molecular mechanism of what causes it and how to help the
tissue heal better is not known," Mohan says.

Another condition that could benefit from a better understanding of
Schwann cells' behavior is dry eye. While temporary dry eye is common,
for some it can be a chronic condition in which the corneal nerves
feel irritated.

"Therapeutics are discovered by knowing which genes have to be
activated or which ones have gone berserk that need to be subdued,"
Mohan says. "What are these genes that are present in the Schwann cell
doing when the cornea is injured? And from there, you ask the question,
could you support nerve injury healing by either activating a gene
or inhibiting something that has gone bad?" Better understanding of
the Schwann cell genes and the proteins they encode could lead to, for
example, a topical drop that could support wound healing by inhibiting
these targeted proteins.


========================================================================== Story Source: Materials provided by University_of_Connecticut. Original
written by Chris DeFrancesco. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Paola Bargagna‐Mohan, Gwendolyn Schultz, Bruce Rheaume,
Ephraim F.

Trakhtenberg, Paul Robson, Sonali Pal‐Ghosh, Mary Ann
Stepp, Katherine S. Given, Wendy B. Macklin, Royce Mohan. Corneal
nonmyelinating Schwann cells illuminated by single‐cell
transcriptomics and visualized by protein biomarkers. Journal of
Neuroscience Research, 2020; DOI: 10.1002/jnr.24757 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/11/201123161034.htm

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