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Igor Nasonkin, Hal Sternberg, Francois Binette, Oscar Cuzzani, Michael West, Ratnesh Singh; Comparison of developmental dynamics in human fetal retina and human pluripotent stem cell derived retinal tissue.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5559.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal degenerative diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are incurable blinding conditions, severely impacting quality of life and affecting millions of people. Finding efficient treatment for these devastating diseases is among the greatest unmet clinical needs. Retinal replacement strategy can bring a piece of healthy mutation-free human retina into a patient’s eye to replace degenerated retinal tissue. The only donor tissue, which was demonstrated to work in animals with retinal degeneration as well as in RP patients is human fetal retinal tissue. However, fetal retina has limited availability and ethical constraints. The 3D retinal tissue (retinal organoids) derived from human pluripotent stem cells (hPSCs) shares many similarities with human fetal retina and may be an excellent replacement of fetal retinal tissue in retinal transplantation experiments. The aim of this study is to find similarities and differences in distribution and expression of molecular markers in human fetal retina and in hPSC-derived 3D retinal tissue.
To assess the similarities between fetal retina and hPSC derived 3D retinal tissue we used immunohistochemistry and RNA-Seq methods. For RNA-Seq analysis total RNA preparations were isolated from human fetal retina (week 8 to 16) and hPSC-derived 3D retinal tissue (week 6-8 and week 10-12).
Preliminary results showed high correlation in gene expression profiles between human fetal retina and hPSC derived 3D retinal tissue. Immunohistochemical profiling of developing human fetal retinal tissue 8 -16 weeks showed strong expression of retinal pigment epithelium (RPE) markers (EZRIN, Beta-catenin), retinal progenitor markers (OTX2, CRX, PAX6), photoreceptor marker (RCVRN), amacrine marker (CALB2) and ganglion marker (BRN3B).
Our study will streamline the development of hPSC-3D retinal tissue (retinal organoid) technologies aimed at repairing and replacing human retina affected by degeneration and causing irreversible blindness.
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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