Intravitreal delivery of rAAV2-hSyn-hRS1 results in Retinal Ganglion Cell-specific gene expression and retinal improvement in the Rs1-KO mouse.

X-linked retinoschisis (XLRS) is a monogenic recessive inherited retinal disease which clinically manifests retinal schisis cavities and disproportionate reduction of b-wave amplitude to the a-wave amplitude. Currently there are no approved treatments while the causal agent was identified as the retinoschisin (RS1). In the last decade, gene therapy has got great progress and given hopes to incurable genetic diseases. Preclinical studies demonstrated the treatment benefits of hRS1 gene augmentation therapy in the mouse models. However, clinical outcomes are dissatisfied which may attribute to the dysfunctional assembly and/or the impaired targeted cells. In the preset study, the human synapsin 1 gene promoter (hSyn) was used to control the expression of hRS1 which specifically targets to the retinal ganglion cells and our results confirmed the specific expression and functional assembly. Moreover, our results demonstrated that a single intravitreal injection of rAAV2-hSyn-hRS1 results in architectural restoration of retinal schisis cavities, improvement of vision and well tolerance in the experimental XLRS mouse model. In brief, this study not only supports the clinical development of the rAAV2-hSyn-hRS1 vector in XLRS patients, but also confirms the therapeutic potential of rAAV-based gene therapy in inherited retinal diseases.