

Lipe, a gene discovered by UT Southwestern Medical Center researchers, appears to be critical to retinal health, with mutations causing immune activity and retinal degeneration. This is significant because the retina detects the light that is turned into vision. The findings, published in Communications Biology, offer light on the mechanisms underlying a variety of retinal illnesses, 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 noted that his laboratory has long been interested in discovering genes that are important for retinal health. These researchers collaborated with the lab of Bruce Beutler, M.D., Professor of Immunology and Internal Medicine at UTSW and Director of the Center for the Genetics of Host Defense. Dr. Beutler was awarded the Nobel Prize in Physiology or Medicine in 2011 for his work on the activation of innate immunity.
Much of Dr. Beutler’s research has made use of a technique known as forward genetics, in which a chemical is used to cause random mutations in mouse genes. Researchers can identify the genes responsible for diverse consequences by examining how these mutant animals differ from animals that do not have the mutations and then studying their genomes.
Dr. Beutler and his colleagues used forward genetics to create approximately 6,000 mutant mice, which Dr. Ufret-Vincenty’s team tested for immune activation markers in the retina. They eventually discovered numerous genes, including Lipe, that when mutated caused these mice to acquire noticeable spots in the fundus, or the back of the eye. Further study revealed that these spots were caused by immune activity known as microglia that had gathered beneath the retina.
The researchers focused on Lipe, which is involved in lipid metabolism, and utilized a genetic approach to disable its activity in another group of mice. Their findings revealed that mice lacking a functional Lipe gene also displayed fundus spots, indicating that this gene serves an unanticipated role in regulating immunological activity in the retina. Further research revealed that when Lipe was turned off, the outer layers of the retina deteriorated, resulting in visual loss in these animals over time.
According to Dr. Ufret-Vincenty, it is unknown why the loss of Lipe function resulted in an immunological response and, ultimately, eyesight loss in these animal models. Additional trials revealed that the lipid balance in the eyes of the affected mice differed significantly from that of wild type mice, which the researchers intend to study further in future research. The researchers also intend to investigate if Lipe has a function in retinal degeneration in diabetic animal models.
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