New research published in the Journal of Biological Chemistry has identified a potential indicator behind a protein that is known to cause blindness.
Talk about this protein.
ABCA4, a protein transporter, is located along the edge of specialized photoreceptor cells within the retina. It typically works to remove N-retinylidene-phosphatidylethanolamine (N-Ret-Pe)— fatty retinal compounds that, due to reactive elements, are also very toxic—out of the eye.
Despite their toxicity, these compounds are also essential to ensuring the eye is functioning properly, up until the point where buildup of the compounds can result in vision loss in diseases such as Stargardt disease.
Now talk about this research.
Researchers sought to determine how ABCA4 malfunctions to cause vision loss and, once they determined the process, transformed the protein transporter’s composition to mimic the effects of Stargardt mutations.
What did they find?
They discovered that part of a protein (called the binding pocket) that interacts with N-Ret-PE is motionless in some Stargardt patients.
As a result, the fatty retinal compounds fall out of the ABCA4 transport and are unable to be removed from the retina, potentially leading to an early onset and severe form of Stargardt.
What’s next?
According to researchers, they are continuing to study ABCA4 by using two types of technologies that can potentially alter the protein transporter: one originally developed to specifically correct DNA with gene-editing approaches, with the second coupling lipid nanoparticles (similar to those leveraged to generate the COVID-19 vaccines) to encapsulate mRNA.
Significance?
The goal, according to study author Robert Molda, PhD, is that by combining the two technologies, “we envision being able to potentially correct the defects in individuals with Stargardt's disease that have specific point mutations," he said.