Long-suspected cause of blindness from eye disease disproved

Vision scientists long have thought that lack of very long chain fatty acids in photoreceptor cells caused blindness in children with Stargardt type 3 retinal degeneration, an incurable eye disease. But researchers at the University of Utah's John A. Moran Eye Center have shown in a new study that lack of these fatty acids does not cause blindness, meaning that the search for the mechanism that robs sight from children with the disease must start anew.

Researchers led by David Krizaj, Ph.D., associate professor of ophthalmology and visual sciences at the Moran Eye Center, bred mice that lacked fatty acids in their photoreceptor cells and to their surprise found that the mice's eyesight was normal. "There was no defect in their daytime or nighttime vision," Krizaj says. "The lack of very long chain fatty acids does not appear to compromise vision in itself."

The research was published March 11, 2013, in PNAS online. Peter Barabas, Ph.D., a at the Moran Eye Center, is first author on the study.

Stargardt disease is a form of macular degeneration that strikes about one in 10,000 children between the ages of 6 and 20. There is no treatment for the disease, although there is evidence that nutrition supplements and protecting eyes from might be beneficial in slowing the progression of blindness.

There are three types of Stargardt disease caused by three different gene mutations. (Paul Bernstein, M.D., Ph.D., professor of ophthalmology and visual sciences and a co-author in the PNAS study, discovered one of the mutations in a Utah family.) Type 3, a rare dominant form of Stargardt disease, is caused by a mutation in ELOVL4, a gene that encodes an enzyme that helps to make fatty acids obtained through our diet into forms that can be incorporated into cell membranes. The mutation displaces the enzyme from its location in an intracellular organelle called endoplasmic reticulum into the cell , which blocks the synthesizing of very long chain fatty acids in photoreceptor cells. But proving that the lack of these fatty acids actually causes blindness has been difficult to show in experiments, because mice in which the ELOVL4 was knocked out did not survive.

Krizaj and his colleagues overcame that problem by engineering mouse models that lacked ELOVL4 only in their photoreceptor cells, allowing the mice to survive but with the fatty acids in those cells reduced up to 90 percent. This allowed them to test directly whether loss of very long chain fatty acids replicates vision loss observed in children with Stargardt's disease. As they report in the journal, electrophysiological and behavioral testing of daytime and night vision in genetically engineered mice showed that sight was not affected despite the dramatic reduction in very in .

Researchers now must look for a different cause of Stargardt type 3. "If it's not the loss of fatty acids causing the disease, then we'll have to find other strategies to help these kids," Krizaj says.

One possibility, according to Krizaj, is that mutated proteins, escaping from the endoplasmic reticulum are aggregating in the cytoplasm causing large deposits consisting of mutated and normal proteins, which is "almost like causing photoreceptor cell death by blocking intracellular traffic and clogging the cells' drains."

Related Stories

The 'see food' diet

date Jul 23, 2009

Current research suggests that a diet high in omega-3 fatty acids may help prevent one of the leading causes of legal blindness among the elderly. The related report by Tuo et al, "A high omega-3 fatty acid diet reduces retinal ...

Fish oil reduces effectiveness of chemotherapy

date Sep 12, 2011

Researchers at University Medical Center Utrecht, the Netherlands, have discovered a substance that has an adverse effect on nearly all types of chemotherapy - making cancer cells insensitive to the treatment. Chemotherapy ...

Recommended for you

Miniature pump regulates internal ocular pressure

date Jul 01, 2015

Elevated or diminished eye pressure impairs our ability to see, and in the worst cases, can even lead to blindness. Until now, there has been no effective long-term treatment. In response, Fraunhofer researchers are developing ...

Closing the Australian eye health gap may be in sight

date Jun 30, 2015

Three years after the launch of the roadmap to close the gap for vision, progress has been made but "much remains to be done", according to the authors of a Perspective published online today by the Medical Jo ...

Pioneering gene therapy takes aim at inherited blindness

date Jun 29, 2015

Canada's first human gene therapy trial for eyes—the replacement of a faulty gene with a healthy one—is now underway at the Royal Alexandra Hospital to preserve and potentially restore vision for people ...

Iris research focuses on blood vessel patterns

date Jun 29, 2015

The structure of the microvasculature or blood vessels in the iris could play an important role in people's contraction of eye maladies like glaucoma and cataract, according to a WA-led study.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.