Abstract
The newt, a urodele amphibian, has an outstanding ability– even as an adult –to regenerate a functional retina through reprogramming and proliferation of the retinal pigment epithelium (RPE) cells, even though the neural retina is completely removed from the eye by surgery. It remains unknown how the newt invented such a superior mechanism. Here we show that disability of RPE cells to regenerate the retina brings about a symptom of proliferative vitreoretinopathy (PVR), even in the newt. When Pax6, a transcription factor that is re-expressed in reprogramming RPE cells, is knocked down in transgenic juvenile newts, these cells proliferate but eventually give rise to cell aggregates that uniformly express alpha smooth muscle actin, Vimentin and N-cadherin, the markers of myofibroblasts which are a major component of the sub-/epi-retinal membranes in PVR. Our current study demonstrates that Pax6 is an essential factor that directs the fate of reprogramming RPE cells toward the retinal regeneration. The newt may have evolved the ability of retinal regeneration by modifying a mechanism that underlies the RPE-mediated retinal disorders.
Highlights
The newt, a urodele amphibian, has an outstanding ability– even as an adult –to regenerate a functional retina through reprogramming and proliferation of the retinal pigment epithelium (RPE) cells, even though the neural retina is completely removed from the eye by surgery
RPE stem cells (RPESCs) are subsequently divided into two cell populations which undergo proliferation, so that they can differentiate in the correct polarity into two epithelial layers of progenitor cells that eventually regenerate new functional neural retina (NR) and RPE, respectively[3]
We addressed whether impairment of retinal regeneration by Pax[6] KD in RPE cells resulted in the appearance of symptoms of RPE-mediated retinal disorders
Summary
The newt, a urodele amphibian, has an outstanding ability– even as an adult –to regenerate a functional retina through reprogramming and proliferation of the retinal pigment epithelium (RPE) cells, even though the neural retina is completely removed from the eye by surgery. RPESCs are subsequently divided into two cell populations which undergo proliferation, so that they can differentiate in the correct polarity into two epithelial layers of progenitor cells (named pro-NR and pro-RPE layers) that eventually regenerate new functional NR and RPE, respectively[3] It remains unknown how such a sophisticated mechanism for retinal regeneration evolved in the newt. Regenerating NR originating from the CMZ (arrow heads) had covered a large area of the RPE before the central RPE cells reached Stage E1 (right-hand box) to E2 (left-hand box) (n = 7) The images in these boxes are enlarged in (e,f) respectively.
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