Fig. 6.

Graphical description of the proposed stages of lens regeneration in Pleurodeles waltl. Lens regeneration staging was modified from Sato’s stages (Sato, 1940; Yamada, 1977). Prior to injury iPECs are terminally differentiated adult somatic cells and at rest in G₀. Following lentectomy, the aqueous and vitreous chambers are disrupted by the lentectomy and fill with extracellular matrix (appears as condensed and compact fibers and sheets)[Sato’s stage 0]. Also at this time, immune and blood cells migrate into the injured area. Subsequently, the iPECs re-enter the cell cycle (transition from G₀ to G₁) [Sato’s stage I]. Extracellular remodeling also starts at this time. Soon after, the iPECs at the tip of the dorsal iris become depigmented while extracellular matrix remodeling continues to takes place [Sato’s II]. The depigmented iPECs proliferate and differentiate into lens cells giving rise to an early lens vesicle. These cells start synthesizing lens specific proteins such as Crystallins [Sato’s stage III-IV]. At this time extracellular matrix is mostly removed from the eye chambers. Cells of the lens vesicle continue to proliferate. Cells located in the inner wall of the lens vesicle start to elongate [Sato’s stage IV-V]. The remaining iPECs that were partially depigmented start to withdraw from the cell cycle. As lens morphogenesis continues, internal cells differentiate into primary lens fibers, and the lens epithelial cells on the anterior side proliferate [Sato’s stage VI-VII]. Next, the primary lens fibers start to lose their nucleus and other organelles and assume a concentric arrangement [Sato’s stage VIII]. Lens epithelial cells at the equatorial zone differentiate giving rise to secondary lens fibers. During this time, iPECs cease proliferation and start to resynthesize their melanosomes [Sato’s stage VIII-IX]. Almost all lens fibers lose their nucleus and other organelles, except the newly formed fibers at the outer region near the lens equator. The regenerating lens detaches from the dorsal iris and assumes a position at the center of the eye [Sato’s stage X-XI].