Disease in a Dish Model

RGCs generated from human iPS cellsRegenerative Medicine for Glaucomatous Degeneration: One of the most practical uses of the iPS cell technology for regenerative medicine is the creation of disease in a dish model of intractable neurodegenerative diseases. Glaucoma is one such disease, where RGC progressively and irreversibly degenerate. One of the prominent risk factors in the disease is the high intraocular pressure (IOP), which is thought to initiate degenerative changes. However, one third of glaucoma patients have normal IOP and yet their RGCs degenerate, which taken together suggest that RGCs are intrinsically vulnerable in glaucoma. Since RGCs are born embryonically and glaucoma is primarily an adult onset disease the knowledge about RGC susceptibility to degeneration, which holds the key to understanding the disease process and formulating therapeutic approaches, remains speculative and rudimentary. The patient-specific induced pluripotent stem cell (iPSC) technology in 2D and 3D (organoid) offers a practical approach to study glaucomatous RGC pathology, from developmental and functional perspectives in a dish allowing gene and drug discoveries for better diagnosis, treatment, and prevention of glaucoma. We are using this approach in both 2D and 3D (organoid) formats to (1) understand RGC and optic nerve development, (2) understand the pathology of glaucomatous RGC degeneration associated with single nucleotide polymorphism (e.g., SIX6 risk allele) and gene mutation (e.g., MyoC mutation), (3) correct RGC defect and degeneration by gene editing, (4) establish microfluidic model of rodent and human optic nerve regeneration, (5) develop the microfluidic model of glia/endothelial cells-RGC interactions, and (6) understand the role of glial (microglia, Muller glia, and astrocytes) inflammasomes and exosomes in RGC degeneration and regeneration.
The figure shows RGCs generated from human iPS cells (image: Pooja Teotia)