June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Rapid entry of RPE and Müller glia cells into the cell cycle following rod-specific ablation in Xenopus laevis
Author Affiliations & Notes
  • Reyna Martinez-De Luna
    Ophthalmology, SUNY Upstate Medical University, Syracuse, New York, United States
  • René Y. Choi
    Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Christine M. Ly
    Ophthalmology, SUNY Upstate Medical University, Syracuse, New York, United States
  • Andrea Sophia Viczian
    Ophthalmology, SUNY Upstate Medical University, Syracuse, New York, United States
  • Michael Zuber
    Ophthalmology, SUNY Upstate Medical University, Syracuse, New York, United States
  • Footnotes
    Commercial Relationships   Reyna Martinez-De Luna, None; René Choi, None; Christine Ly, None; Andrea Viczian, None; Michael Zuber, None
  • Footnotes
    Support  NIH Grant EY015748 (MEZ) and Lions District 20-Y1 (CML)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5396. doi:
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    • Get Citation

      Reyna Martinez-De Luna, René Y. Choi, Christine M. Ly, Andrea Sophia Viczian, Michael Zuber; Rapid entry of RPE and Müller glia cells into the cell cycle following rod-specific ablation in Xenopus laevis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5396.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The retinal pigment epithelium (RPE) and the ciliary marginal zone (CMZ) are established sources of regenerated retina in amphibians following retinectomy. However, mechanical removal of the retina to initiate regeneration may have concealed other potential sources of new retinal cells. We previously demonstrated rod photoreceptors regenerate following rod-specific ablation. Here we determine which retinal cell types enter the cell cycle following rod loss and if only rods are generated as part of the regenerative response to rod-specific ablation.

Methods : Rod photoreceptors were specifically ablated by metronidazole (Mtz) treatment of XOPNTR transgenic tadpoles, which were then allowed to recover for up to 30 days. Cycling cells were labeled with EdU or BrdU. The number and identity of EdU+ or BrdU+ retinal cells was determined by immunolabeling retinal sections at different time points during regeneration with RPE65 (RPE cells); R5 (Müller glia); XAP2/transducin (rods); calbindin (cones); calretinin (Bipolar, subsets of Amacrine and RGCs); Pax6 (retinal progenitors); PCNA (S-phase).

Results : We identified cycling Müller glia (R5+/BrdU+) and RPE (RPE65+/BrdU+) cells in the central retina 7 days after rod ablation. Cycling RPE cells were sometimes still pigmented, while cycling Müller cells were often clustered with BrdU+ cells not expressing the Müller glial marker R5. Müller glia and RPE cells also expressed the cell cycle marker PCNA, and the retinal progenitor marker Pax6. After 30 days recovery, BrdU+ rods and cones were detected in the ONL, while regenerated bipolar cells (Calretinin+/BrdU+) were detected in the central INL. BrdU+ mature cell types were never detected in the central retina of Mtz-treated wild-type or untreated XOPNTR animals. In the CMZ, rod ablation resulted in the production of twice as many BrdU+ cells relative to controls. Interestingly, we did not observe a significant increase in the proportion of rods generated from the CMZ.

Conclusions : We demonstrate for the first time that, following rod-specific ablation, Müller glia and RPE enter the cell cycle and become Pax6+ in the X. laevis retina. We show rod death is sufficient to activate a proliferative response from the retinal progenitors of the CMZ. Furthermore, newborn cells are not restricted to a rod fate, since other retinal cell types were also generated in the central and peripheral retina.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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