Abstract
Cataract is a leading cause of blindness worldwide. Currently, restoration of vision in cataract patients requires surgical removal of the cataract. Due to the large and increasing number of cataract patients, the annual cost of surgical cataract treatment amounts to billions of dollars. Limited access to functional human lens tissue during the early stages of cataract formation has hampered efforts to develop effective anti-cataract drugs. The ability of human pluripotent stem (PS) cells to make large numbers of normal or diseased human cell types raises the possibility that human PS cells may provide a new avenue for defining the molecular mechanisms responsible for different types of human cataract. Towards this end, methods have been established to differentiate human PS cells into both lens cells and transparent, light-focusing human micro-lenses. Sensitive and quantitative assays to measure light transmittance and focusing ability of human PS cell-derived micro-lenses have also been developed. This review will, therefore, examine how human PS cell-derived lens cells and micro-lenses might provide a new avenue for development of much-needed drugs to treat human cataract.
Highlights
Cataract is a condition in which light transmission through the ocular lens is decreased, resulting in reduced vision and blindness
Human pluripotent stem (PS) cell-derived organoids, have the potential to provide new and powerful tools for elucidating molecular mechanisms of disease progression that are specific to individual disease risk factors, as well as associated drug discovery studies [14,15,16]
Micro-lenses treated with high Vx-770 concentrations lost their ability to transmit and focus light [17]. These findings suggest human PS cell-derived, ROR1-expressing lens epithelial cells (LECs) and micro-lenses could aid identification of the specific, initiating cataract molecular mechanisms that result from different cataract risk factors
Summary
Cataract is a condition in which light transmission through the ocular lens is decreased, resulting in reduced vision and blindness. The ability to define the initiating molecular mechanisms of human cataract formation—and, effective treatments to inhibit or delay cataract progression—has largely been hampered by the lack of access to functional human lens tissue at the initial stages of cataract formation. The ability of human pluripotent stem (PS) cells to (i) self-renew and (ii) differentiate into any cell type of the body, means human PS cells can provide a large-scale source of normal or diseased human cells for research [1,2,3,4]. Human PS cells are enabling new research approaches into human cell and tissue development, elucidation of molecular disease mechanisms, drug discovery and toxicity assessments, and investigation of candidate cell-based therapies. This review will explore how human PS cell technology is being applied to cataract research, with particular emphasis on cataract disease modelling, drug discovery and toxicity assessment
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