Mutations in the RS1 gene, which encodes retinoschisin, cause X-linked juvenile retinoschisis, a retinal dystrophy in males. Retinoschisin specifically interacts with the retinal sodium-potassium adenosine triphosphatase (Na/K-ATPase), a transmembrane ion pump. Na/K-ATPases also bind cardiac glycosides, which control the activity of the pump and have been linked to disturbances in retinal homeostasis. In this study, we investigated the crosstalk between retinoschisin and cardiac glycosides at the retinal Na/K-ATPase and the consequences of this interplay on retinal integrity.

Given the high morbidity and mortality among children in low- and middle-income countries as a result of preventable causes, the U.S. government and the United Nations Children's Fund convened an Evidence Summit on Enhancing Child Survival and Development in Lower- and Middle-Income Countries by Achieving Population-Level Behavior Change on June 3-4, 2013, in Washington, D.C. This article summarizes evidence for technological advances associated with population-level behavior changes necessary to advance child survival and healthy development in children under 5 years of age in low- and middle-income countries. After a rigorous evidence selection process, the authors assessed science, technology, and innovation papers that used mHealth, social/transmedia, multiplatform media, health literacy, and devices for behavior changes supporting child survival and development. Because of an insufficient number of studies on health literacy and devices that supported causal attribution of interventions to outcomes, the review focused on mHealth, social/transmedia, and multiplatform media. Overall, this review found that some mHealth interventions have sufficient evidence to make topic-specific recommendations for broader implementation, scaling, and next research steps (e.g., adherence to HIV/AIDS antiretroviral therapy, uptake and demand of maternal health service, and compliance with malaria treatment guidelines). While some media evidence demonstrates effectiveness in changing cognitive abilities, knowledge, and attitudes, evidence is minimal on behavioral endpoints linked to child survival. Population level behavior change is necessary to end preventable child deaths. Donors and low- and middle-income countries are encouraged to implement recommendations for informing practice, policy, and research decisions to fully maximize the impact potential of mHealth and multimedia for child survival and development.

Mutations in the RS1 gene encoding retinoschisin cause X-linked juvenile retinoschisis (XLRS), a hereditary retinal dystrophy in males. While most of the XLRS associated mutations strongly interfere with cellular secretion, this is not true for mutants RS1-F108C, -R141G, -R141H, -R182C, -H207Q and -R209H. Native retinoschisin builds double-octamers and binds to retinal membranes, interacting with the retinal Na/K-ATPase. Functionally, it regulates MAP kinase signaling and Na/K-ATPase localization, and hampers photoreceptor degeneration. In this study, we investigated the capacity of the retinoschisin mutants still secreted extracellularly to fulfil these tasks. We addressed secretion and oligomerization of the heterologously expressed mutants as well as their binding to recombinant retinal Na/K-ATPases and murine retinoschisin-deficient (Rs1h-/Y) retinal and non-retinal explants. This has refined the categorization of secreted retinoschisin mutants: (i) no octamerization, unspecific membrane binding (RS1-F108C and -R182C), (ii) double-octamerization but no membrane binding (RS1-R141H), and (iii) double-octamerization and unspecific membrane binding (RS1-R141G, -H207Q, and -R209H). Notably, selected mutants of all categories (RS1-F108C, -R141H, and -R209H) failed to regulate retinal MAP kinase signaling and Na/K-ATPase localization in Rs1h-/Y retinal explants, and could not attenuate photoreceptor degeneration. Bioinformatic modeling of the secreted mutants depicted prominent alterations in the spatial and temporal conformation of a substructure called "spike 3" and its vicinity, implying a crucial role of this substructure for binding capacity and specificity. Taken together, our data point to a pathomechanism for secreted retinoschisin mutants, specifically to disturbances of the retinoschisin interface accompanied by unphysiological membrane interactions and impaired regulatory functions.