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Home/Health/Gene that regulates immune activity in the retina identified
Health


GENE THAT REGULATES IMMUNE ACTIVITY IN THE RETINA IDENTIFIED

NewsPico5 days ago
0 122 3 minutes read
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Newswise — DALLAS – July 11, 2023 – UT Southwestern Medical Center researchers
have identified a gene called Lipe that appears to be pivotal to retinal health,
with mutations spurring immune activation and retinal degeneration. This is
important because the retina is responsible for detecting the light that is
transformed into vision. The findings, published in Communications Biology,
provide clues about the mechanisms behind a variety of disorders affecting the
retina, including macular degeneration and diabetic retinopathy.

“Many retinal diseases are associated with activation of immune cells in the
retina. We’re showing that Lipe could play an important role in controlling this
process,” said study leader Rafael Ufret-Vincenty, M.D., Associate Professor
of Ophthalmology at UTSW.

Dr. Ufret-Vincenty explained that his lab has long been interested in
identifying genes essential to retinal health. To accomplish that goal, these
researchers teamed up with the lab of Bruce Beutler, M.D., Professor
of Immunology and Internal Medicine and Director of the Center for the Genetics
of Host Defense at UTSW. Dr. Beutler received the 2011 Nobel Prize in Physiology
or Medicine for his discoveries involving the activation of innate immunity.

Much of Dr. Beutler’s work has taken advantage of an approach called forward
genetics, in which a chemical is used to induce random mutations in the genes of
mice. By identifying how these mutant animals differ from animals that don’t
carry the mutations and then studying their genomes, researchers can identify
the genes responsible for various effects.

Using forward genetics, Dr. Beutler and his colleagues generated nearly 6,000
mutant mice, which Dr. Ufret-Vincenty’s team screened for markers of immune
activation in the retina. Eventually, they identified several genes
including Lipe that, when mutated, caused these animals to develop spots visible
in the fundus, or the back of the eye. Further investigation showed these spots
were activated immune cells known as microglia that collected underneath the
retina.

Narrowing their focus to Lipe, which plays a role in lipid metabolism, the
researchers used a genetic technique to turn off its function in another group
of mice. Their results showed that mice without a functioning Lipe gene also had
fundus spots, confirming that this gene plays an unexpected role in regulating
immune activity in the retina. Further investigation showed that when Lipe was
inactivated, the outer layers of the retina degenerated, causing vision loss in
these animals over time.

Dr. Ufret-Vincenty said it’s unclear why the loss of Lipe function led to an
immune reaction and, ultimately, vision loss in these animal models. Additional
experiments showed that the balance of lipids in the eyes of the affected mice
differed significantly from wild type mice, a clue the researchers plan to
investigate in future research. The researchers also plan to study
whether Lipe plays a role in retinal degeneration in mouse models of diabetes.

Other UTSW researchers from the Department of Ophthalmology who contributed to
this study were first author Seher Yuksel, Ph.D., Postdoctoral Researcher;
Bogale Aredo, Ph.D., Senior Research Scientist; Yeshumenesh Zegeye, B.S.,
Research Assistant; John D. Hulleman, Ph.D., Assistant Professor; and Igor A.
Butovich, Ph.D., Associate Professor. Additional collaborators were Laurent
Gautron, Ph.D., Assistant Professor, Internal Medicine; and Center for the
Genetics of Host Defense members Miao Tang, M.D., Instructor, Xiaohong Li, M.D.,
Ph.D., Assistant Professor, Sara Ludwig, Ph.D., Assistant Professor, and Eva
Marie Moresco, Ph.D., Assistant Professor.

Dr. Beutler is a Regental Professor and holds the Raymond and Ellen Willie
Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie,
Sr.

This research was funded by grants from the National Eye Institute
(1R01EY033181, R01EY027349), the National Eye Institute Center Core Grant for
Vision Research (P30EY030413), the National Institutes of Health (R01AI125581,
U19AI100627), the VanSickle Family Foundation, UT Southwestern Synergy Grant,
and the David M. Crowley Foundation; and by the Josephine Long Biddle Chair in
Age-Related Macular Degeneration Research, the Lillian and James Cain Endowment
in Vision Loss, the Anne Marie and Thomas B. Walker Jr. Fund for Research on
Macular Degeneration, and the Department of Ophthalmology at UTSW.

About UT Southwestern Medical Center  
UT Southwestern, one of the nation’s premier academic medical centers,
integrates pioneering biomedical research with exceptional clinical care and
education. The institution’s faculty has received six Nobel Prizes, and includes
26 members of the National Academy of Sciences, 19 members of the National
Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The
full-time faculty of more than 2,900 is responsible for groundbreaking medical
advances and is committed to translating science-driven research quickly to new
clinical treatments. UT Southwestern physicians provide care in more than 80
specialties to more than 100,000 hospitalized patients, more than 360,000
emergency room cases, and oversee nearly 4 million outpatient visits a year.







Tags
All Journal News Diabetes Genetics Immunology Macular Degeneration National Eye
Institute (NEI) National Institutes of Health (NIH) Nature (journal) Newswise UT
Southwestern Medical Center Ut Southwestern;Ut Southwestern Medical Center;Basic
Science;Center for the Genetics of Host Defense;General Internal
Medicine;Internal Medicine;Immunology;Ophthalmology Vision
NewsPico5 days ago
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