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Using stem cells to research eye disease

Affiliated with the University of MelbourneUniversity of Melbourne Logo

The following article was written by Drs Alex Hewitt and Alice Pébay and explains the potential of stem cells in the study of eye diseases.

Large-scale generation of induced pluripotent stem cells for the modelling and correction of blinding diseases

Principal investigators: Dr Alex Hewitt, Clinical Genetics & Dr Alice Pébay, Neuroregeneration

The extreme difficulty in obtaining ocular tissue from living people currently represents a major barrier to developing new treatments for blinding disease. Recent breakthroughs in stem cell technology have led to the ability to generate stem cells from adult tissue, and these “induced pluripotent stem cells” (iPSCs) now represent a powerful disease modelling tool. Generating iPSCs directly from patients allows cells to be differentiated into specific cells of interest for disease modeling, drug screening, and understanding of fundamental pathogenic mechanisms.

We have the established techniques and methodologies to efficiently generate patient-specific retinal pigmented epithelium cells, which are dysfunctional in age-related macular degeneration (AMD) and inherited retinal dystrophies as well as retinal ganglion cells, which are affected in glaucoma and other optic neuropathies. We are now modeling these ocular conditions in a dish, using iPSCs derived from specific patients in order to establish the molecular events leading to disease progression.

We have recently acquired an automated platform that will allow the generation of hundreds of patient specific retinal cells, originally derived from their skin biopsy. This novel approach is used for the large-scale modeling of diseases with complex genetics such as glaucoma and AMD, by next generation sequencing for the in-depth molecular profiling of the transcriptome. This novel approach will potentially lead to new targets for novel treatments to prevent common and devastating diseases.

We are also using gene editing technology for correction of monogenic diseases of the retina and the optic nerve. The CRISPR system is used by bacteria to counter viral intrusion and has recently been adapted to allow efficient editing of the mammalian nuclear genome. CRISPR-based technology is being heralded as a relatively straightforward technology for in vitro correction of genetic mutations in patient-specific cells and is particularly attractive for treating inherited diseases caused by genes with very specific spatial and stoichiometric expression, such as that found in many of the retinal dystrophies. We are using our unique cohort of patients with distinct monogenic inherited retinal dystrophies and iPSC technology to directly study the utility of genomic editing and correction.