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Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract in vitro

Patricia A Murphy,M. Kabir,Tarini Srivastava,Michele Mason,Chitra Dewi,Seakcheng Lim,A. Yang,Djordje Djordjević,M. Killingsworth,J. Ho,D. Harman,Michael D. O’Connor

Published 2018 in Development

ABSTRACT

ABSTRACT Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified, including drug treatments, age, smoking and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here, we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening and for clinically relevant toxicity assays. Highlighted Article: Using human pluripotent stem cells, robust and reliable methods are described for large-scale production of purified human lens epithelial cells, and for subsequent large-scale generation of clinically relevant, light-focusing micro-lenses.

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