Stargardt disease is the most common inherited cause of macular degeneration, but patients who lose the same gene, ABCA4, don’t all lose their vision the same way. A new dataset digs into why.
Researchers built two mouse models of ABCA4 loss: one mimicking a noncoding human variant, the other carrying a misfolded, catalytically dead protein. The two responded differently to two candidate drugs — maraviroc, which targets inflammation, and AdipoRon, which targets ceramide metabolism — a hint that treatment choice may need to match mutation type.
To trace the biology behind this, the team ran single-cell RNA-seq on retinal cells from wild-type, knockout, and knock-in mice, before and after light-induced bleaching, with and without drug treatment: 27 samples in all. The result is a resource for matching therapy to mutation, and a benchmark for testing future gene-editing treatments.
