Cell signaling pathways in vertebrate lens regeneration

Abstract

Certain vertebrates are capable of regenerating parts of the eye, including the lens. Depending on the species, two principal forms of in vivo lens regeneration have been described wherein the new lens arises from either the pigmented epithelium of the dorsal iris or the cornea epithelium. These forms of lens regeneration are triggered by retinal factors present in the eye. Studies have begun to illuminate the nature of the signals that support lens regeneration. This review describes evidence for the involvement of specific signaling pathways in lens regeneration, including the FGF, retinoic acid, TGF-beta, Wnt, and Hedgehog pathways.

Figure 1

Examples of various animals capable of regenerating the lens of the eye. A). The newt Cynops pyrrhogaster (the Japanese Fire Belly Newt). B). The cobitid fish, Misgurnus anguillicaudatus (the Japanese Weather Loach) C). The tadpole larvae of the frog Xenopus laevis (the South African Clawed Frog). See text for further details. Scale bar equals 7mm for A, 15mm for B and 6mm for C.

Figure 2

Diagrams illustrating the two main processes of lens regeneration. A–D). Steps involved in Wolffian lens regeneration that take place in certain newts and salamanders. This process takes place within the dorsal iris of the adult eye following removal of the lens (B) (i.e., the new lens is derived from pigmented iris epithelial cells that undergo transdifferentiation). Dashed arrows in B and C indicate key retinal signals that support the process of lens regeneration. E–H). Steps involved in cornea lens regeneration that takes place in frogs of the genus Xenopus and the salamander Hynobius unnangso. The process takes place within cells of the basal layer of the larval cornea epithelium following removal of the lens and perforation of the cornea endothelium (F). Dashed arrows in F and G indicate key retinal signals that support the process of lens regeneration.

Figure 3

Highly simplified summary diagrams of various signaling pathways known to play roles during vertebrate lens regeneration. Various pathways and pathway members are as labeled. Not all known elements are included here for the sake of simplicity. Specific activators and inhibitors used to manipulate these pathways are also included, and specific synthetic agents are enclosed in ovals. See text for further details.