Regeneration of neural retina and lens from retina pigment cell grafts in adult newts

Stone, L. S.; Steinitz, H.

doi:10.1002/jez.1401350206

Cited by 37 publications

(9 citation statements)

References 10 publications

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“…If the retina is experimentally removed in these animals, the RPE loses pigmentation, proliferates and generates two new epithelial layers: a pigmented layer and a non-pigmented layer. The non-pigmented layer begins to express genes typical of retinal progenitor cells and undergoes extensive cell division to produce a new retina (Keefe, 1973a,b;Nagy, 1987, 1989;Stone, 1950;Stone and Steinitz, 1957). In vitro experiments, and transplantation experiments have demonstrated that the RPE is the source of neural retinal tissue , and this phenomenon was one of the first well-recognized examples of ''transdifferentiation'' (Okada, 1981).…”

Section: Introductionmentioning

confidence: 95%

Activin signaling limits the competence for retinal regeneration from the pigmented epithelium

Sakami

Etter

Reh

2008

Mechanisms of Development

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Regeneration of the retina in amphibians is initiated by the transdifferentiation of the retinal pigmented epithelium (RPE) into neural progenitors. A similar process occurs in the early embryonic chick, but the RPE soon loses this ability. The factors that limit the competence of RPE cells to regenerate neural retina are not understood; however, factors normally involved in the development of the eye (i.e. FGF and Pax6) have also been implicated in transdifferentiation. Therefore, we tested whether activin, a TGFbeta family signaling protein shown to be important in RPE development, contributes to the loss in competence of the RPE to regenerate retina. We have found that addition of activin blocks regeneration from the RPE, even during stages when the cells are competent. Conversely, a small molecule inhibitor of the activin/TGFbeta/nodal receptors can delay, and even reverse, the developmental restriction in FGF-stimulated neural retinal regeneration.

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Section: Introductionmentioning

confidence: 95%

Activin signaling limits the competence for retinal regeneration from the pigmented epithelium

Sakami

Etter

Reh

2008

Mechanisms of Development

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“…Thus, although the RPE differentiates into a polarized epithelial sheet, it originates from precursors that also give rise to the neural retina. Perhaps because of this origin, RPE cells from embryonic chicken retina (2, 3) and from amphibian retina (4,5) retain the ability to take on neuronal characteristics and to transdifferentiate into neural retina. Thus, when placed in cell culture, embryonic RPE cells organize into layered structures similar to embryonic neural retina and express neuronal markers (3, 6).…”

mentioning

confidence: 99%

Voltage-dependent sodium channels develop in rat retinal pigment epithelium cells in culture.

Botchkin

Matthews

1994

Proc. Natl. Acad. Sci. U.S.A.

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Whole-cell patch-clamp recordings were made from isolated cells of the retinal pigment epithelium (RPE) of neonatal rats. After 24 hr in cell culture, RPE cells developed a transient, voltage-activated inward current that was never observed in acutely isolated cells. The kinetics, voltage-dependence, and reversal potential of the current and its dependence on external sodium demonstrated that the current was due to the expression of voltage-activated Na+ channels in cultured RPE cells. The current was partly blocked by tetrodotoxin at low concentrations (<100 nM), but a second component of Na+ current was unblocked by tetrodotoxin at concentrations up to 10 IAM. Nab channels were present in cultured RPE cells at sufficient density to support regenerative action potentials in voltage recordings. Both the epithellal cells of the RPE and the neurons of the retina derive embryonically from neural origin, and it is known that under certain circumsances, nonmammalian RPE cells retain the ability to take on neuronal characteristics. The development of voltage-activated Na+ channels and the presence ofaction potentials demonstrate that neonatal mammalian RPE cells are also capable of expressing neuronal characteristics in cell culture.The retina consists of two major subdivisions: a multistratified neuronal portion and a monocellular epithelial sheet, the retinal pigment epithelium (RPE). Both the neural retina and the RPE derive embryonically from the neural plate (1). Thus, although the RPE differentiates into a polarized epithelial sheet, it originates from precursors that also give rise to the neural retina. Perhaps because of this origin, RPE cells from embryonic chicken retina (2, 3) and from amphibian retina (4,5) retain the ability to take on neuronal characteristics and to transdifferentiate into neural retina. Thus, when placed in cell culture, embryonic RPE cells organize into layered structures similar to embryonic neural retina and express neuronal markers (3, 6). In addition, under appropriate conditions the RPE in vivo can be induced to transform into neural retina (7-9).In this paper, we report that cultured RPE cells from neonatal rats express voltage-activated Na+ channels and can produce action potentials, properties normally associated with neurons. Voltage-gated Na+ currents were not seen in acutely isolated RPE cells but developed within 24 hr after the cells were placed in low-density cell culture. Thus, the electrophysiological character of the cells rapidly changed in culture from epithelial to neuronal. The expression of voltage-dependent Na+ channels is likely a manifestation of the transdifferentiation of epithelial cells into neuronal cells. METHODSCell Preparation. RPE cells were isolated from albino or pigmented rats 6-8 days old by the method of Li and Turner (10). Whole eyes were incubated for 55-70 min at 370C in Hanks' balanced salt solution (HBSS) with collagenase at 78 units/ml (Sigma type IV) and hyaluronidase at 40 units/ml (Sigma type I-S), followed by 50-65 min in HBSS/0....

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“…Down-regulation in the retina implies that this tissue is involved in lens regeneration or that it is affected by the absence of the lens. Older experiments have shown that when the neural retina is separated from the dorsal iris or when dorsal iris is left devoid of retina, lens regeneration is inhibited (Stone, 1958 ;Stone and Steinitz, 1957 ;Stone and Gallagher, 1958 ;Reyer, 1977). A role of retina in lens regeneration has also been implied by different experiments.…”

Section: Discussionmentioning

confidence: 94%

Regulation of Homeobox-containing Genes during Lens Regeneration

Jung

Rio‐Tsonis

Tsonis

1998

Experimental Eye Research

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Regeneration of neural retina and lens from retina pigment cell grafts in adult newts

Cited by 37 publications

References 10 publications

Activin signaling limits the competence for retinal regeneration from the pigmented epithelium

Activin signaling limits the competence for retinal regeneration from the pigmented epithelium

Voltage-dependent sodium channels develop in rat retinal pigment epithelium cells in culture.

Regulation of Homeobox-containing Genes during Lens Regeneration

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