The Genetic Mutations of Macular Degeneration

Study precisely maps the location of disease causing mutations.

Researchers mapped out and identified the precise location of mutations that cause X-linked Retinoschisis (XLRS), which may lead to new treatment options.

XLRS is a genetic disease that precedes a type of macular degeneration where the retina’s inner layers split, resulting in severe vision loss and gradual blindness.

In a new study published in Human Molecular Genetics, researchers undertook a structural analysis of the disease, which develops from mutations in the retinal protein retinoschisin.

Retinoschisin is a protein that plays a crucial role in the cellular organization of the retina by assembling itself to form paired octameric rings, which resembles an 8-bladed propeller.

For the study, researchers examined the paired rings, as well as the effects on the rings of the 2 XLRS-causing mutations by using a cryo-electron microscope.

The cryo-electron microscopy gave researchers the ability to identify the location of the mutations on the rings.

“We found that one disease-causing mutation sits in the interface between the octamer rings, causing retinoschisin to be less stable,” said lead study author Clair Baldock. “The other mutation is on the propeller tip which we think is a novel interaction site for other binding proteins in the retina.”

The study authors noted that these findings provide hope that future work could lead to genetic interventions and treatments, thus preventing or limiting the damage caused by XLRS.

“XLRS is a promising candidate for gene therapy, so our findings on these 2 different classes of mutations will be informative for future therapeutic strategies,” Baldock said.