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R. I. Martinez, H. M. El-Hodiri; Retinal Progenitor Cells Mediating Retinal Regeneration in Pre-Metamorphic Xenopus Laevis Are Not Exclusively of Rpe Origin. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5035. doi: https://doi.org/.
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Following partial resection, the retina of pre-metamorphic Xenopus laevis can regenerate. Retinal regeneration in other species such as fish, chickens as well as in adult X. laevis has been described to occur through dedifferentiation of a pigmented epithelium or glial cells. The purpose of this study is to characterize regeneration in the X. laevis retina after damage and investigate the source of new cells in the regenerating retina.
A nasal-dorsal segment was resected from the retina of stage 44 tadpoles. Regeneration was analyzed by histology. In situ hybridization was performed on sectioned regenerating retinas to examine the expression of Rx, Pax6, Sox2, Notch and NeuroD. Immunohistochemistry was done on paraffin retinal sections for islet-1, rhodopsin and RPE-65.
X. laevis tadpoles can regenerate the retina after resection. We have analyzed retinal regeneration and found it is essentially complete 30 days after resection. Shortly after injury, the wound is repopulated by proliferating retinal progenitor cells (RPCs). These cells have the characteristic morphology of RPCs, and are organized across a gradient of maturity similar to those described in the X. laevis ciliary marginal zone (CMZ). In our analysis, 38% of the regenerating retinas analyzed showed RPE-65 immunoreactivity in the RPCs that repopulate the wound and give rise to new retina. In the absence of damage, the expression of the RPE-specific marker, RPE-65, is only found in the RPE and not in neural retina. We did not observe RPE-65 immunoreactivity in the CMZ progenitors or in any other cells of the regenerating retinas.
Transdifferentiation of the RPE is the major source of regenerating cells in newt, early embryonic chick, mouse, and adult X. laevis. In zebrafish and chickens, Müller glia proliferate and dedifferentiate to give rise to new cells after retinal damage. Our results suggest that RPE transdifferentiation contributes to retinal regeneration in pre-metamorphic X. laevis. Based on these results, we propose a model of regeneration where RPCs repopulate the damaged retina and organize according to a gradient of maturity, similar to the progenitors of the CMZ. We propose that these RPCs are not exclusively derived from transdifferentiating RPE cells. This suggests that, in contrast to other systems, multiple cell types contribute to retinal regeneration in X. laevis tadpoles.
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