Abstract
Purpose:
Autophagy is a process whereby cellular components are recycled through the formation of autophagosomes that ultimately fuse with lysosomes where their contents are degraded. Previous studies have shown that the lens expresses the full complement of genes required for autophagy and that autophagy can be induced in lens cells. The transparent function of the lens depends on degradation of mitochondria and other organelles during lens development and lens cell differentiation. Here, we determined the levels of autophagosomes throughout the developing and adult lens and we determined whether mitochondria were specifically degraded by autophagy during lens cell maintenance and differentiation.
Methods:
Adult human and embryonic chick lenses were examined by transmission electron microscopy and by dual color confocal microscopy. Autophagosomes and mitochondria were identified by structural analysis and reaction with autophagosomal- and mitochondrial-specific antibodies. Autophagosomal degradation of mitochondria was induced in primary chick lens cells upon serum starvation and increased mitochondrial degradation monitored.
Results:
Autophagosomes are present in large numbers throughout the adult human and developing chick lens. Large numbers of intact and partially degraded mitochondria were detected within autophagosomes in both lens epithelium and in lens fiber cells. Autophagy-mediated degradation of lens cell mitochondria was induced upon serum starvation.
Conclusions:
Here we show that autophagy is a major function of the adult and developing lens. We demonstrate that mitochondria are degraded in both embryonic and adult lens epithelium and differentiating fiber cells by autophagy in a process also called mitophagy. Since lens organelle degradation is essential for lens cell differentiation and transparency, autophagy and mitophagy are therefore essential for lens development and prevention of cataract formation.
Keywords: 500 differentiation •
497 development •
600 mitochondria