Journal News

JLR: Sphingolipids and retinal degeneration

Dawn Hayward
Sept. 1, 2016

Two uses for the same drug. It’s been done before with success. Take aspirin, which alleviates pain and is a blood thinner. Or Wellbutrin, which helps smokers quit and is an antidepressant. In a recently published paper in the Journal of Lipid Research, researchers took a multiple sclerosis drug called Gilenya from Novartis and gave it a new use: treatment of retinal degeneration.

Gilenya, a multiple sclerosis drug, may have a new use as a treatment for retinal degeneration.

Why Gilenya? Gilenya, which also goes by the name FTY720, initially was used in multiple sclerosis, a central nervous system disorder involving the destruction of certain nerve cells. Gilenya is an altered version of a natural product and has immunosuppressive effects, particularly through the blockade of sphingolipid synthesis. This last point is key, as retinal degeneration also is known to involve sphingolipid biosynthesis.

Retinal degeneration is a catchall term for a group of diseases whose hallmark is photoreceptor cell death. This cell death has many contributing factors, one of which is ceramide, a sphingolipid whose role in retinal degeneration has been investigated by the group of Nawajes Mandal at the University of Oklahoma Health Sciences Center. In fact, in previously published work, the Mandal group identified ceramide as a critical player in retinal degeneration by using Gilenya in a rat model of light-induced retinal degeneration.

In the current JLR study, Mandal and colleagues turned their focus to a laboratory rat model, one which more frequently is used in the retinal degeneration field. This rat model closely matches how retinal degeneration happens in humans. Using this popular model gives a better idea of the effects of the drug. These transgenic animals start losing their sight at post-natal day 22 and have 50 percent photoreceptor death at postnatal day 45. This occurs because they have a mutated rhodopsin gene.

The investigators administered Gilenya to these rats at both the early and late stages of the disease and examined eye health, gene expression and sphingolipid levels. With early dosing of Gilenya came improved rod and cone function as well as lowered ceramide biosynthesis gene expression, two positive signs of improvement. In addition, the investigators noticed that the sphingolipid profile, a feature that was altered in the disease model, was reset, and they observed normal levels of associated enzymes were observed with Gilenya administration.

While Gilenya may appear to be a winner for retinal degeneration treatment, many questions remain. First, the exact pathway between ceramide biosynthesis and photoreceptor cell death needs to be established. Second, the precise mechanism of action of Gilenya also needs to be established. And, of course, many more studies with this drug in animal models have to be completed.

Still, this study makes a significant contribution to the search for retinal- degeneration drugs. Treatments for this disease are few and far between, and beginning with a Food and Drug Administration-approved drug is a good start to alleviating this disorder.

Dawn Hayward

Dawn Hayward earned a Ph.D. in biochemistry from the Johns Hopkins University School of Medicine

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

Part 2: ‘Aha moments’ essay contest honorable mentions
Contest

Part 2: ‘Aha moments’ essay contest honorable mentions

May 13, 2021

To celebrate our three journals going open access, we invited readers to share their moments of discovery in science. Here are three honorable mentions.

The impacts of COVID-19 on women’s physical health
Health Observance

The impacts of COVID-19 on women’s physical health

May 11, 2021

Pregnancy, periods, long COVID and side effects: lots of questions remain unanswered.

An abundance of potential
Observance

An abundance of potential

May 10, 2021

For National Lipid Day, a new contributor offers a glance at what yeast might yield.

Astrocyte cells in the fruit fly brain are an on-off switch
News

Astrocyte cells in the fruit fly brain are an on-off switch

May 9, 2021

Adaptable neurons are tied to learning and memory but also to neurological disorders. By studying fruit flies, researchers found a mechanism that controls neuroplasticity.

Part 1: ‘Aha moments’ essay contest honorable mentions
Contest

Part 1: ‘Aha moments’ essay contest honorable mentions

May 6, 2021

To celebrate our three journals going open access, we invited readers to share their moments of discovery in science. Here are two honorable mentions.

From the journals: MCP
Journal News

From the journals: MCP

May 6, 2021

Using silver nanoparticles to target cancer. Glycosylation of SARS-CoV-2. Characterizing the glycan signature in tumor tissue. Read about recent papers in the journal Molecular & Cellular Proteomics.