Regeneration of the amphibian retina: Role of tissue interaction and related signaling molecules on RPE transdifferentiation

Abstract

Regeneration of eye tissue is one of the classic subjects in developmental biology and it is now being vigorously studied to reveal the cellular and molecular mechanisms involved. Although many experimental animal models have been studied, there may be a common basic mechanism that governs retinal regeneration. This can also control ocular development, suggesting the existence of a common principle between the development and regeneration of eye tissues. This notion is now becoming more widely accepted by recent studies on the genetic regulation of ocular development. Retinal regeneration can take place in a variety of vertebrates including fish, amphibians and birds. The newt, however, has been considered to be the sole animal that can regenerate the whole retina after the complete removal of the retina. We recently discovered that the anuran amphibian also retains a similar ability in the mature stage, suggesting the possibility that such a potential could be found in other animal species. In the present review article, retinal regeneration of amphibians (the newt and Xenopus laevis) and avian embryos are described, with a particular focus on transdifferentiation of retinal pigmented epithelium. One of the recent progresses in this field is the availability of tissue culture methods to analyze the initial process of transdifferentiation, and this enables us to compare the proliferation and neural differentiation of retinal pigmented epithelial cells from various animal species under the same conditions. It was revealed that tissue interactions between the retinal pigmented epithelium and underlying connective tissues (the choroid) play a substantial role in transdifferentiation and that this is mediated by a diffusible signal such as fibroblast growth factor 2. We propose that tissue interaction, particularly mesenchyme-neuroepithelial interaction, is considered to play a fundamental role both in retinal development and regeneration.

Embryonic stem cells and retinal repair

“…In both instances, members of the fibroblast growth factor (FGF) family of molecules have been demonstrated to be of clear importance (Araki, 2007;Moshiri et al, 2004). For instance, basic FGF (bFGF) initiates the transition from neuroepithelium towards neuroretinal phenotype in chick (Pittack et al, 1997(Pittack et al, , 1991 and expression of FGF9 in embryonic mouse RPE results in conversion of these cells into neural retina .…”

Retinal pigment epithelium development, plasticity, and tissue homeostasis

“…As we now know, the origins and identities of the regenerative cell sources vary widely across species (Barbosa-Sabanero et al, 2012; Lamba et al, 2008; Locker et al, 2010; Nelson and Hyde, 2012). With respect to RPE transdifferentation into retina, urodele amphibians, anuran amphibians, and embryonic chick stand out because they show bona-fide metaplasia in vivo without the addition of exogenous factors and they generate all major retinal cells classes through dedifferentiation, proliferation, and activation of retinal neurogenic programs (for reviews, see (Araki, 2007; Barbosa-Sabanero et al, 2012; Lamba et al, 2008; Reh and Levine, 1998); refer to Chiba/El-Hodiri in this issue). RPE to retina transdifferentiation during adult stages appears to be specific to amphibians with it best documented in urodeles (i.e.…”

Shared Triggering Mechanisms of Retinal Regeneration in Lower Vertebrates and Retinal Rescue in Higher Ones

“…Fibroblast growth factor basic (FGF2) is one of several agents that elicits most profound effects in RPE and NR cells. Since 9 0 s t h e r o l e o f F G F 2 i n R P E t r a n s d i f f e r e ntiation and NR regeneration after RPE↔NR separation in adult amphibians and bird embryos is received the intensive study (Araki, 2007;Mitsuda et al, 2005;Park & Hollenberg, 1993). In accordance with the data including our own, FGF2 and FGF2R coupled with that of transcription factor Pax6 control urodelean RPE cell dedifferentiation and proliferation after NR removal (Avdonin, 2010;Chiba & Mitashov, 2007).…”