Administering Accutane, a drug commonly used to treat acne, UCLA researchers have successfully stopped the accumulation of toxic pigments in the eyes of animals with a genetic defect similar to Stargardt’s macular degeneration. The UCLA team gave a daily injection of Accutane to mimic the effect of constant light deprivation and the results proved dramatic. These toxic pigments, called lipofuscin, are responsible for the visual loss in patients with Stargardt’s disease.
UCLA Researchers Find Common Acne Treatment Stops Blindness in Animal Model
Date: March 17, 2003
Contact: Kirsten Holguin ( firstname.lastname@example.org )
Administering Accutane, a drug commonly used to treat acne, UCLA researchers have successfully stopped the accumulation of toxic pigments in the eyes of animals with a genetic defect similar to Stargardt’s macular degeneration. The UCLA team gave a daily injection of Accutane to mimic the effect of constant light deprivation and the results proved dramatic.
These toxic pigments, called lipofuscin, are responsible for the visual loss in patients with Stargardt’s disease.
“Given the similarities between the mouse model and humans with Stargardt’s, it seems likely that Accutane will suppress lipofuscin from accumulating in Stargardt’s patients,” said Dr. Gabriel Travis, professor of ophthalmology and biological chemistry at the David Geffen School of Medicine at UCLA. “These results should lead to human clinical trials with Stargardt’s patients.”
The basic science discovery is reported in the March 17 online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences (www.pnas.org/).
Stargardt’s is part of a group of macular degeneration diseases that share the common symptom of central visual loss. It is an inherited disease affecting about one in 10,000 people. Stargardt’s is sometimes referred to as juvenile macular degeneration because the patients are young when the symptoms start, usually before puberty.
Vision loss occurs when the central part of the retina, called the macula, deteriorates, causing a blurred area in the center of a person’s field of vision. The loss of vision can be gradual or rapid and varies from patient to patient. Peripheral vision is often unaffected.
Earlier research had identified the gene that causes Stargardt’s as ABCR. The gene defect disrupts a protein that normally works to flush out all-trans-retinaldehyde, a byproduct of vision, from photoreceptors in the retina. Photoreceptors, called rods and cones, are specialized cells that are sensitive to light. As a result of the defect, toxins build up in the retinal pigment epithelium, or RPE, a layer of cells near the retina that plays a critical role in the survival of photoreceptor cells.
The research team’s previous work had also shown that raising Stargardt’s mice in total darkness blocked the toxic buildup in the animals’ eyes. The team’s understanding of the biochemical defect in Stargardt’s disease suggested a possible treatment using Accutane, which has a side effect of night blindness.
In the latest research, Travis’ research team hypothesized that Accutane may prevent the accumulation of toxins in the eyes of mice with Stargardt’s. A chemical in the toxins, called A2E, poisons the RPE cells. Since the RPE supports the photoreceptors, when the RPE vanishes, so do the rods and cones found in the photoreceptors causing central vision loss in the animal models.
Armed with this knowledge, the UCLA team in the current study administered a daily injection of Accutane to mimic the effect of constant light deprivation.
The results proved dramatic. When they examined the mice after two months of treatment, the researchers found that the toxins had stopped accumulating in the eyes. The treatment had no effect on daylight vision in these mice.
“Our findings suggest that Accutane will suppress the accumulation of lipofuscin pigments in Stargardt’s patients. Our next step will be to test the drug in clinical trials to establish its safety and effectiveness in people,” Travis said.
Travis cautioned that Stargardt’s patients should not take Accutane on their own until human clinical trials determine a safe and effective dosage.
“Accutane would likely be ineffective at best, and possibly harmful, in patients with other forms of retinal degeneration besides Stargardt’s,” he said.
The study was funded with grants from the National Eye Institute, the Foundation Fighting Blindness, the Ruth and Milton Steinbach Fund and the Macula Vision Research Foundation.
The Jules Stein Eye Institute at UCLA is a world-recognized leader in patient care, education and research. The institute records more than 70,000 visits each year from patients with all categories of eye diseases and disorders and consistently ranks as the No. 1 eye care center in the western United States in U.S. News & World Report’s annual survey of best hospitals.
– The Jules Stein Eye Institute: jsei.org/
– National Eye Institute: www.nei.nih.gov/
– Foundation Fighting Blindness: www.blindness.org/
– Macula Vision Research Foundation: www.mvrf.org/