hiPSC-based Model Systems

Experimental model systems are required to study retinal disease pathology. To this end, we have established a cell repository of patient derived induced pluripotent stem cells (iPSC). We routinely obtain skin fibroblasts or peripheral blood mononuclear cells from retinal dystrophy patients and healthy individuals. In our laboratory, these adult cells are reprogrammed to iPSC using a plasmid-based approach. Over the years, we have built up an extensive repository of iPSC from around 50 individuals, including patients with age-related macular degeneration (AMD), Best disease, various gene-specific retinitis pigmentosa subtypes and Sorsby fundus dystrophy. To model the retinal diseases in vitro, we differentiate the iPSC lines into multiple retinal cell systems. To this end, we perform various differentiation protocols to generate 2-dimensional cellular monolayers of retinal pigment epithelium cells (RPE), endothelial cells or choroidal endothelial cells. We also employ a differentiation protocol that produces 3-dimensional highly complex cellular structures known as retinal organoids. Retinal organoids contain multiple cell types native to the retina including rod and cone photoreceptors, horizontal cells, ganglion cells, and RPE. The iPSC-based model systems allow investigations into consequences of genetic mutations in a cell culture-based system thereby giving unprecedented insight into inherited retinal diseases.