Molecular Bases of Disease
The selective estrogen receptor modulator raloxifene mitigates the effect of all-trans-retinal toxicity in photoreceptor degenerationThe retinoid cycle is a metabolic process in the vertebrate retina that continuously regenerates 11-cis-retinal (11-cisRAL) from the all-trans-retinal (atRAL) isomer. atRAL accumulation can cause photoreceptor degeneration and irreversible visual dysfunction associated with incurable blinding retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and atrophic age-related macular degeneration (AMD). The underlying cellular mechanisms leading to retinal degeneration remain uncertain, although previous studies have shown that atRAL promotes calcium influx associated with cell apoptosis.
Rescuing Trafficking Mutants of the ATP-binding Cassette Protein, ABCA4, with Small Molecule Correctors as a Treatment for Stargardt Eye DiseaseBackground: Mutations in nucleotide binding domain 1 of ABCA4 cause Stargardt Disease.Results: Correctors rescue trafficking of NBD1 mutants by altering a proteostatic network of quality control proteins.Conclusion: Rescue of trafficking ABCA 4 mutants can be accomplished by correctors similar to CFTR.Significance: There is currently no treatment for Stargardt macular degeneration.