The link between inhibition of PI3K signaling, induction of autophagy, and elimination of organelles to form the lens organelle-free zone

The elimination of organelles to create the lens organelle-free zone (OFZ) is a macroautophagy/autophagy-dependent mechanism that occurs without causing cell death. This process is essential to the ability of the lens to focus incoming images on the retina, as the presence of these organelles would interfere with lens refraction of light and impair vision. Therefore, organelles are removed from differentiating lens fiber cells during development, their elimination beginning with the non-nuclear organelles in the central lens fiber cells, and expanding over time to the neighboring fiber cells in the lens cortex. The removal of fiber cell nuclei lags behind that of non-nuclear organelles, following the same spatiotemporal patterning. We find that removal of organelles to form the OFZ depends on the induction of autophagy through the inhibition of phosphoinositide 3-kinase (PI3K) signaling. Abbreviation OFZ– organelle-free zone