June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Characterization of retinal pigment epithelial cells in rd1 mouse model of retinal degeneration
Author Affiliations & Notes
  • Murilo F Roggia
    Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine of the University of Tokyo, Tokyo, Japan
  • Yasuo Noda
    Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine of the University of Tokyo, Tokyo, Japan
  • Takashi Ueta
    Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine of the University of Tokyo, Tokyo, Japan
  • Footnotes
    Commercial Relationships Murilo Roggia, None; Yasuo Noda, None; Takashi Ueta, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3642. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Murilo F Roggia, Yasuo Noda, Takashi Ueta; Characterization of retinal pigment epithelial cells in rd1 mouse model of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3642.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: In many patients with inherited retinal degeneration, various genetic defects hamper the survival of photoreceptors. Although future therapeutic strategies including the delivery of repaired genes and photoreceptors might depend on the integrity of retinal pigment epithelium (RPE), it has not been sufficiently evaluated yet. In the present study we investigated the alterations in the RPE cells of rd1 mouse model of retinal degeneration.

Methods: RPE flatmounts were immunostained for ZO-1 and occludin for the evaluation of morphological characteristics of RPE in rd1 mice in comparison to those in WT mice. Real-time RT-PCR and western blot was used to evaluate the protein level of mesenchymal markers in RPE of rd1 mice in comparison to those of WT mice. To test a hypothesis that mesenchymal characterization in RPE cells of rd1 mice may be implicated in the progression of retinal degeneration, inhibitors of TGF-β family signaling (SB431542; ALK4/5/7 inhibitor and LDN193189; ALK2/3 inhibitor) were administered intravitreally, and the extent of photoreceptor degeneration was assessed morphologically.

Results: RPE cells in rd1 mice were very distinct from those in the WT mice. Not only the size of the RPE cells of rd1 mice presented a significant variability, the shape of the cells was also considerably irregular. Contrarily, wild mice showed a regular hexagonal shape and similar size of the RPE cells. The mRNA and protein levels of mesenchymal markers, and TGF-β1 and TGF-β2 were upregulated in RPE cells of rd1 mice compared to those of WT mice. Interestingly, Expressions of epithelial markers were preserved in RPE cells of rd1 mice. Furthermore, we found that the intravitreal injections of TGF-β inhibitors suppressed the progression of retinal degeneration in rd1 mice compared to vehicle treatment.

Conclusions: In rd1 mice, the RPE cells show an acquirement of mesenchymal characteristics while they maintain expressions of epithelial markers. TGF-β family signaling might be implicated in the pathogenesis of retinitis pigmentosa.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×