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Deliang Zhu, Mengyuan Xie, Zekai Cui, Yonglong Guo, Shiwei Liu, Peiyuan Wang, Jun Zhang, Jiansu Chen; Transplantation of human iPS-derived RPE cells preserves the retinal structure and function in the rd10 mouse model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2883. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is most common retinal degenerative disease. Human induced pluripotent stem (iPS) cells derived retinal pigment epithelium (hiPS-RPE) cells provide seed cells for RP. We investigate the effect of hiPS-RPE cells on rd10 mice retinal degeneration model.
1. Differentiation of human iPS cells towards RPE through cultured in differentiation medium with sequential addition of defined factors. 2. hiPS-RPE cells labeled with PKH26 and spheroid culture 3 days before transplantation. Postnatal day12 (P12) rd10 mice received sub-retinal injections of dissociated hiPS-RPE cells (2×104/eye). 3. Morphological analysis were performed after 14-day treatments of hiPS-RPE at P26 rd10 mice. 4. Analysis of ocular condition in rd10 mice by immunofluorescent, TUNEL and Western blot. 5. ERG response were used to analyze visual function.
1.RPE cells were induced from hiPS cells through sequential differentiated condition. 2. Dissociated hiPS-RPE cells after spheroid culture were able to maintain young status, viability and anti-apoptosis. 3. The implanted hiPS-RPE cells survived well in rd10 mouse retina. The outer nuclear layer (ONL) dramatically thinner by 30% in rd10 retinas (3±1.5nuclei/column) while hiPS-RPE treated rd10 retinas had thicker ONL by 50% (6±1.5 nuclei/column) (n=5,*p=0.012). But ONL in wild type retinas was the most thick one (12±1.5 nuclei/column). 4. rd10 retina presented 60% CD68 positive microglia, while implanted group rd10 retina presented 20% CD68 positive microglia (n=3, *p=0.04). There were 10 TUNEL-positive cells of photoreceptors in implanted group and those 28 in control group ( n=3, *p=0.03). 5. Scotopic and Photopic ERG responses to 0.03,0.3,1 and 10 cd-s/m2 light intensities, at the same light intensity implanted group a-wave and b-wave amplitude were approximately twice as large as compared with control group (n=5, **p=0.001).
Our study suggests that hiPS-RPE cells enable to persevere the structural and functional features of ONL photoreceptors, which is a potential therapy for retinal degenerative diseases and paves the way for further research and human trials.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
hiPS-RPE cells treatment reduces rd10 mouse retinal photoreceptor apoptosis.
hiPS-RPE cell preserved the rd10 mice visual function detected by ERG.
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