What causes Stargardt disease?

The retina contains light-sensing cells called photoreceptors. There are two types of photoreceptors: rods and cones. Together, rod and cones detect light and convert it into electrical signals, which are then “seen” by the brain. Rods are found in the outer retina and help us see in dim and dark lighting. Cones are found in the macula and help us see fine visual detail and color. Both cones and rods die away in Stargardt disease, but for unclear reasons, cones are more strongly affected in most cases.

You may have heard about the importance of vitamin A-rich foods in maintaining healthy vision. That’s because vitamin A is needed to make key light-sensitive molecules inside photoreceptors. Unfortunately, this manufacturing process can lead to harmful vitamin A byproducts — which turn out to play a key role in Stargardt disease.

Mutations in a gene called ABCA4 are the most common cause of Stargardt disease. This gene makes a protein that normally clears away vitamin A byproducts inside photoreceptors. Cells that lack the ABCA4 protein accumulate clumps of lipofuscin, a fatty substance that forms yellowish flecks. As the clumps of lipofuscin increase in and around the macula, central vision becomes impaired. Eventually, these fatty deposits lead to the death of photoreceptors and vision becomes further impaired.

Mutations in the ABCA4 gene are also associated with other retinal dystrophies including cone dystrophy, cone-rod dystrophy, and retinitis pigmentosa, a severe form of retinal degeneration.READ MORE