In this study, state of the art sequencing technologies were used to identify disease-causing mutations in the USH2A gene in an adult patient with autosomal recessive Retinitis Pigmentosa. Induced pluripotent stem cells (iPSCs), generated from the patient's skin, were differentiated into multi-layer eyecup-like structures with features of human retinal cells. The inner layer of the eyecups contained immature photoreceptor cells that expressed photoreceptor markers and exhibited cilia and basal bodies characteristic of outer segments.

Mutations in ABCA4 cause Stargardt disease and other blinding autosomal recessive retinal disorders. However, sequencing of the complete coding sequence in patients with clinical features of Stargardt disease sometimes fails to detect one or both mutations. For example, among 208 individuals with clear clinical evidence of ABCA4 disease ascertained at a single institution, 28 had only one disease-causing allele identified in the exons and splice junctions of the primary retinal transcript of the gene.

The purpose of this study was to determine whether a xeno-free synthetic cell culture surface (Synthemax™) could be used to aid in the production and subsequent retinal specific differentiation of clinical grade induced pluripotent stem cells (iPSCs). iPSCs were generated using adult somatic cells via infection with either a single excisable lentiviral vector or 4 separate non-integrating Sendai viruses driving expression of the transcription factors OCT4, SOX2, KLF4, and c-MYC.

The Research Eye Bank at the IVR enables scientists to study common and rare diseases. Scientists at the IVR recently had the first opportunity to characterize eyes from a donor with retinal degeneration due to mutations in the ABCA4 gene. This work, which combined human genetics with histology and state of the art microarray analysis, found that death of photoreceptor cells (rods and cones) occurs in advance of death of the retinal pigment epithelium (RPE).