Purpose: Our previous study observed that human induced pluripotent stem cell (HiPSC)-derived lentoid bodies (LBs) became cloudy with extended culture time, partially mimicking the progress of human age-related
cataracts (
ARCs) in a dish. In the present study,
lanosterol, a potential anticataract
drug, was used to further verify the value of this model in
drug screening for
cataract treatment. Methods: Mature LBs on day 25, which were differentiated from HiPSCs using the "fried egg" method, were continually cultured and treated with either
dimethyl sulfoxide (control) or
lanosterol. The LBs' shape and opacity alterations were examined using light microscopy and mean gray value evaluation. The soluble and insoluble
proteins were examined through SDS-PAGE gel electrophoresis combined with
Coomassie blue staining. The
protein aggregations were examined with immunofluorescence. Results: The mature LBs became cloudy with an extended culture time, and the opacification of the LBs was partially prevented by
lanosterol treatment. There was less increase in insoluble
proteins in the
lanosterol-treated LBs than in the control group. There were also fewer cells containing aggregated
protein (αA-
crystallin and αB-
crystallin) puncta in the
lanosterol-treated LBs than in the control LBs. Conclusion: It was found that the opacification of LBs could be delayed by
lanosterol treatment, which could be achieved by reducing
protein aggregation, suggesting a promising HiPSC-derived
drug-screening model for Age-related
cataract.