X-linked juvenile Retinoschisis

X-linked juvenile retinoschisis (XLRS) is a degenerative disease of the retina and represents one of the most common forms of early onset macular degeneration in young males. Female carriers, in general, are asymptomatic, with only very few documented cases of subtle retinal changes. XLRS is characterized by a splitting of the retinal layers (schisis) as well as defects in signal transduction between photoreceptors and bipolar cells. Mutations in the RS1 gene, which is specifically expressed in the retina, were shown for the first time by our laboratory to be causative for XLRS. The protein encoded by RS1 was termed retinoschisin and is secreted from photoreceptors and bipolar cells as a homo-octameric complex. Recent studies at our Institute confirmed that retinoschisin specifically and directly interacts with the retinal Na/K-ATPase, a membrane spanning ion pump consisting of the subunits ATP1A3 and ATP1B2. By establishing the retinoschisin-deficient mouse model, we have generated an excellent animal model to mimic human XLRS. In this model we have observed an influence of retinoschisin on Na/K-ATPase localization and Na/K-ATPase-associated intracellular signaling cascades. Applying state-of-the-art experimental designs, the ongoing work is aimed to further elucidate the molecular understanding of a retinal protein that is crucial for ensuring long-term maintenance of retinal architecture and integrity.

Selected publications:

  • Schmid V, Plössl K, Schmid C, Bernklau S, Weber BHF, Friedrich U. Retinoschisin and Cardiac Glycoside Crosstalk at the Retinal Na/K-ATPase. Invest Ophthalmol Vis Sci. 2020 May 11;61(5):1. doi: 10.1167/iovs.61.5.1
  • Plössl K, Schmid V, Straub K, Schmid C, Ammon M, Merkl R, Weber BHF, Friedrich U. Pathomechanism of mutated and secreted retinoschisin in X-linked juvenile retinoschisis. Exp Eye Res. 2018 Dec;177:23-34. doi: 10.1016/j.exer.2018.07.021