Retinal Multipotent Stem-Cell Derived “MiEye” Spheroid 3D Culture Model for Preclinical Screening of Non-viral Gene Delivery Systems

Abstract

Non-viral retinal gene therapy is a promising therapeutic approach towards the management of retinal degenerative diseases especially glaucoma. Current methods of in vitro preclinical screening of candidate nanoparticle systems in monolayer cell cultures are not reliable in predicting in vivo performance. In this paper, we describe the development of a multipotent stem-cell derived three-dimensional “mini-retina” culture model (MiEye) that aims to simulate an in vivo clinical model for more reliable gene delivery system screening. Through the utilization of multiplex gene expression profiling, we have shown that retinal stem cells can be differentiated in 3D culture to generate retinal neurospheres comprising of multiple retinal cell types. The 3D cell culture model combined with confocal microscopy imaging and fluorescence profiling techniques is a powerful tool as a retinal gene and drug delivery screening model.