Long-suspected cause of blindness from eye disease disproved

March 11, 2013

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."

Explore further: Fish oil reduces effectiveness of chemotherapy

Related Stories

Fish oil reduces effectiveness of chemotherapy

September 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 ...

Researchers work to prevent blindness from age-related macular degeneration

May 18, 2011
Slowing down the aggregation or "clumping" of vitamin A in the eye may help prevent vision loss caused by macular degeneration, research from Columbia University Medical Center has found.

Recommended for you

Scientists regenerate retinal cells in mice

July 26, 2017
Scientists have successfully regenerated cells in the retina of adult mice at the University of Washington School of Medicine in Seattle.

Genome editing with CRISPR-Cas9 prevents angiogenesis of the retina

July 24, 2017
A research team from the Schepens Eye Research Institute of Massachusetts Eye and Ear has successfully prevented mice from developing angiogenesis of the retina—the sensory tissue at the back of the eye—using gene-editing ...

Too little vitamin D may hinder recovery of injured corneas

July 24, 2017
Injury or disease in combination with too little vitamin D can be bad for the window to your eyes.

Combination of type 2 diabetes and sleep apnoea indicates eyesight loss within four years

July 4, 2017
Research led by the University of Birmingham has discovered that patients who suffer from both Type 2 diabetes and obstructive sleep apnoea are at greater risk of developing a condition that leads to blindness within an average ...

Nearly 60% of pinkeye patients receive antibiotic eye drops, but they're seldom necessary

June 28, 2017
A new study suggests that most people with acute conjunctivitis, or pinkeye, are getting the wrong treatment.

Magnetic implants used to treat 'dancing eyes'

June 26, 2017
A research team has successfully used magnets implanted behind a person's eyes to treat nystagmus, a condition characterised by involuntary eye movements.

0 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.