A detailed sequence of events for uncontrolled elongation, deformation, and breakdown of protrusions in an AQP0−/− lens. (A, B) The normal formation of two types of protrusions occurs in the absence of AQP0 in young differentiating fibers that may be seen at approximately 40 μm deep (A), but show signs of abnormal elongation at approximately 60 μm deep (B). Under this condition, type 1 (open arrows) and type 2 (arrows) elongated protrusions still exhibit their typical structural characteristics and interlock with each other in a tightly compact fashion (B). (C, D) In deeper fibers at approximately 100 μm deep, while type 1 changes its shape and size, type 2 elongates into tubular structures of uncontrolled length. (D, E) Due to restriction of the extracellular distance between narrow-side fiber cells, many elongated tubular protrusions make recurrent turns and twists to form complex aggregates. (E, F) Type 1 protrusions (open arrows) show significant shape changes and size increases in deeper fibers at approximately 200 μm deep. Both types of protrusions become fragmented, and the interlocking support between protrusions is completely vanished. (G, H) This eventually leads to fiber cell separation and collapse in the deeper cortex at approximately 300 μm deep. Scale bars: 1 μm.