Biomedical subjects
Publications and source records attributed to Matthew W Grogg.
The newt is one of the few organisms that is able to undergo lens regeneration as an adult. This review will examine the signaling pathways that are involved in this amazing phenomenon. In addition to outlining the current research involved in elucidating the key signaling molecules in lens regeneration, we will also highlight some of the similarities and differences between lens regeneration and development.
Lens regeneration in adult newts is a classic example of how cells can faithfully regenerate a complete organ through the process of transdifferentiation. After lens removal, the pigment epithelial cells of the dorsal, but not the ventral, iris dedifferentiate and then differentiate to form a new lens. Understanding how this process is regulated might provide clues about why lens regeneration does not occur in higher vertebrates. The genes six-3 and pax-6 are known to induce ectopic lenses during embryogenesis. Here we tested these genes, as well as members of the bone morphogenetic protein (BMP) pathway that regulate establishment of the dorsal-ventral axis in embryos, for their ability to induce lens regeneration. We show that the lens can be regenerated from the ventral iris when the BMP pathway is inhibited and when the iris is transfected with six-3 and treated with retinoic acid. In intact irises, six-3 is expressed at higher levels in the ventral than in the dorsal iris. During regeneration, however, only expression in the dorsal iris is significantly increased. Such an increase is seen in ventral irises only when they are induced to transdifferentiate by six-3 and retinoic acid or by BMP inhibitors. These data suggest that lens regeneration can be achieved in noncompetent adult tissues and that this regeneration occurs through a gene regulatory mechanism that is more complex than the dorsal expression of lens regeneration-specific genes.
Lens regeneration in newts is a remarkable process, whereby a lost tissue is replaced by transdifferentiation of adult tissues that only a few organisms possess. In this review, we will touch on the approaches being used to study this phenomenon, recent advances in the field of lens regeneration, similarities and differences between development and regeneration, as well as the potential role stem cells may play in understanding this process.
Lens regeneration in adult mice is possible when the lens capsule is left behind after lentectomy. The lens is regenerated by the remaining adherent lens epithelial cells, which differentiate to form lens fibres within days, showing normal morphology and bow regions. Epithelial to mesenchymal cell transformation is also seen during the early stages. The mouse, therefore, can become an indispensable animal model for cataract research, surgery and therapy.