XXXX prevents ex  vivo @entity3236 formation through induction of autophagy-mediated cell death.

@entity8574 @entity9472 @entity235 @entity205 @entity3236
The purpose of this study was to determine the @entity205 ( @entity9472 ) dose and minimum drug delivery time needed to prevent @entity3236 ( @entity3236 ) in an ex  vivo @entity235 model and evaluate the mechanism of @entity9472 -induced cell death. @entity235 lens epithelial cells (LEC) were treated with @entity9472 and changes in cell migration, proliferation, and density were monitored over time. @entity9472 -treated LEC underwent transmission electron microscopy (TEM), immunofluorescence, and immunoblotting in the presence or absence of autophagy inhibitors to evaluate the mechanism of cell death. Lens capsules were harvested from @entity235 cadaver eyes for an ex  vivo model of @entity3236 . Lens capsules were treated with @entity9472 for 1, 2, 3, 4, 5, 6, or 7 days, and subsequently maintained in culture for a total of 28 days in the absence of drug. @entity9472 reduced LEC viability in a dose dependent manner. Morphologically, @entity9472 -treated LEC were swollen, had intact nuclei, lacked peripheral chromatin condensation, and demonstrated prominent vacuolization; TEM revealed autophagosomes. LC3-II protein expression and @entity8574 orange fluorescence increased in @entity9472 -treated cells. A small non-significant induction of cleaved caspase-3 was observed in @entity9472 -treated LEC. Lens capsules treated with 5, 6, or 7 days of 10   g/mL @entity9472 showed a significant decrease in ex  vivo @entity3236 formation; 6 days of drug delivery prevented @entity3236 . This study finds that morphologic changes, formation of acidic vesicles, and increased expression of LC3-II supports the hypothesis that @entity9472 mediates LEC death via autophagy; this is a novel finding in the lens. Induction of @entity9472 -induced apoptosis was minimal. Six days of intracapsular @entity9472 drug delivery prevented ex  vivo @entity3236 formation.
