Skin cells from a patient with retinitis pigmentosa have been used to generate induced pluripotent stem cells, which could potentially form the basis of new treatments for this disease.
High-throughput screening of over 6000 drugs using cells and retina tissue with a CEP290 ciliopathy mutation identified a small molecule, reserpine, which enhanced photoreceptor survival in retinal organoids and in a mouse disease model by partially restoring balance in proteostasis.
The integrated analysis of multi-omics and functional evidence both in vitro and in knock-in mouse models reveal novel gain-of-function pathogenic mechanisms of dominant CRX HD missense mutations.
Using a cross-species phenotypic drug discovery pipeline, compounds promoting rod photoreceptor survival in zebrafish and mouse models of retinitis pigmentosa were identified, evidence of additive effects of paired compounds and inhibition of PARP-dependent cell death suggest novel therapeutic strategies.
Multiple alleles of Txnip, which can interact with several different proteins, including Hsp90AB1, were tested for their ability to prolong the survival of cone photoreceptors in diseases leading to blindness.
Amanda M Travis, Samiya Manocha ... Jillian N Pearring
Dominant mutations in Arl3, linked to inherited retinal dystrophy, disrupt the active Arl3-GTP ciliary gradient and cause a defect in rod photoreceptor nuclear migration that can be rescued by elevating ciliary Arl3 activity or reducing aberrant non-ciliary Arl3 activity.
A combination of in vitro and in vivo experiments demonstrate a cell-autonomous role of the KIT ligand/KIT signaling pathway in protecting retinal photoreceptor cells from environmentally or genetically caused degeneration.
Sangeetha Kandoi, Cassandra Martinez ... Deepak A Lamba
Stem cell-derived retinal organoids are a useful tool to understand the pathobiology of devastating retinal degenerations and can aid to identify and validate therapeutics to promote rescue.
AAV-Txnip prolongs vision in mouse models of blindness, enhancing lactate catabolism, mitochondrial health, and ATP production in a condition that likely has a limited glucose supply.
