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