Retinoschisin 1 (RS1) (RS1)

Retinoschisin 1 (RS1) is a 224-amino acid secreted protein primarily synthesized and secreted by retinal photoreceptors and bipolar cells (UniProt: O15537). It contains a highly conserved discoidin domain that mediates cell-cell adhesion and maintains the structural integrity of the retinal layers (NCBI Gene: 6247). Mutations in the RS1 gene result in X-linked juvenile retinoschisis (XLRS), a leading cause of macular degeneration in young males, characterized by the formation of cystic spaces within the retina and a characteristic reduction in the electroretinogram (ERG) b-wave (PubMed: 30130105). As a monogenic disease, RS1 is a primary target for adeno-associated virus (AAV)-mediated gene replacement therapies (PubMed: 28910511). These therapies, such as Laruparetigene zovadoparvovec (AGTC-501) and ATSN-101, aim to deliver a functional RS1 gene to the retina to restore protein expression and stabilize retinal structure (ClinicalTrials.gov: NCT02416622). Clinical trials are currently evaluating various AAV vectors and delivery methods, including intravitreal and subretinal injections, to treat patients with this inherited retinal degeneration.

Other names

RetinoschisinXLRS1RSX-linked juvenile retinoschisis protein

Gene replacement therapy via viral vector delivery to restore functional retinoschisin protein expression in retinal cells.