iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice

(Stem Cell Reports 8, 69–83, January 10, 2017) After publication of our recent manuscript in Stem Cell Reports (Mandai et al., 2017Mandai M. Fujii M. Hashiguchi T. Sunagawa G.A. Ito S. Sun J. Kaneko J. Sho J. Yamada C. Takahashi M. iPSC-derived retina transplants improve vision in rd1 end-stage retinal degeneration mice.Stem Cell Reports. 2017; 8: 69-83Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar), and as it was kindly suggested by some researchers in the related field, we realized that there was some ambiguous description in the Introduction and some confusion as to which photoreceptors had been used in each study (harvested fetal-, neonatal-, or ES/iPS-derived tissues/cells). We would like to make the following corrections to the text and cite several additional papers as indicated below. First, we would like to add a brief description of the work referenced in the first sentence of the Introduction and include references to the work of Radner et al., 2001; Woch et al., 2001; Sagdullaev et al., 2003; Seiler et al., 2008; and Seiler et al., 2010, replacing the sentence as follows. The original sentence reads “Although fetal retinas have been transplanted into patients with retinal degeneration, there is no conclusive evidence that these transplants can restore visual function.” The corrected text reads “Neonatal and fetal retina sheet transplants are reported to restore activity in host retinal ganglion cells or superior colliculus, a midbrain visual center for motor commands, in some mice and rats with retinal degeneration (Woch et al., 2001Woch G. Aramant R.B. Seiler M.J. Sagdullaev B.T. McCall M.A. Retinal transplants restore visually evoked responses in rats with photoreceptor degeneration.Invest. Ophthalmol. Vis. Sci. 2001; 42: 1669-1676PubMed Google Scholar, Radner et al., 2001Radner W. Sadda S.R. Humayun M.S. Suzuki S. Melia M. Weiland J. de Juan Jr., E. Light-driven retinal ganglion cell responses in blind rd mice after neural retinal transplantation.Invest. Ophthalmol. Vis. Sci. 2001; 42: 1057-1065PubMed Google Scholar, Sagdullaev et al., 2003Sagdullaev B.T. Aramant R.B. Seiler M.J. Woch G. McCall M.A. Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa.Invest. Ophthalmol. Vis. Sci. 2003; 44: 1686-1695Crossref PubMed Scopus (84) Google Scholar), and fetal retinas have been transplanted together with retinal pigment epithelium into patients with retinal degeneration and improved vision in some patients (Radtke et al., 2008). Mechanisms have been suggested as neurotrophic effect (Radner et al., 2001Radner W. Sadda S.R. Humayun M.S. Suzuki S. Melia M. Weiland J. de Juan Jr., E. Light-driven retinal ganglion cell responses in blind rd mice after neural retinal transplantation.Invest. Ophthalmol. Vis. Sci. 2001; 42: 1057-1065PubMed Google Scholar) or synaptic connections between unspecified inner retinal cells of host and graft (Seiler et al., 2008Seiler M.J. Thomas B.B. Chen Z. Wu R. Sadda S.R. Aramant R.B. Retinal transplants restore visual responses: trans-synaptic tracing from visually responsive site in the superior colliculus (SC) labels transplant neurons.Eur. J. Neurosci. 2008; 28: 208-220Crossref PubMed Scopus (43) Google Scholar, Seiler et al., 2010Seiler M.J. Aramant R.B. Thomas B.B. Peng Q. Sadda S.R. Keirstead H.S. Visual restoration and transplant connectivity in degenerate rats implanted with retinal progenitor sheets.Eur. J. Neurosci. 2010; 31: 508-520Crossref PubMed Scopus (52) Google Scholar), but there is no conclusive evidence that photoreceptors in these retina transplants can form functional synapses with host bipolar cells.” Second, we would like to add one reference (here underlined) that was missing, as follows: “These reports, together with a number of reports describing protocols to differentiate retinal tissue from human ESCs or induced pluripotent stem cells (iPSCs) (Kuwahara et al., 2015; Nakano et al., 2012; Zhong et al., 2014Zhong X. Gutierrez C. Xue T. Hampton C. Vergara M.N. Cao L.H. Peters A. Park T.S. Zambidis E.T. Meyer J.S. et al.Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs.Nat. Commun. 2014; 5: 4047Crossref PubMed Scopus (578) Google Scholar)….” Third, we would like to add the underlined words to specify graft source to the second paragraph of the Introduction, as follows: “Recent studies using cell suspensions of postnatal mouse photoreceptor precursors or human ES/iPS derived photoreceptor precursors in end-stage retinas, which have lost the ONL, indicated possible light response by pupillary reflex and behavior tests, although direct evidence of light response from the graft cells or synaptic function is still lacking.” Fourth, also in the second paragraph of the Introduction, we would like to make the following change and add one reference (underlined). The original sentence reads “In addition, retinal grafts in the form of cell suspension or microaggregates did not generally survive for long, whereas a retinal graft sheet in a clinical trial was observed to survive 3 years after the transplantation (del Cerro et al., 2000; Mandai et al., 2012; West et al., 2010).” The corrected sentence reads “In addition, rat fetal retina sheet grafts (Sagdullaev et al., 2003Sagdullaev B.T. Aramant R.B. Seiler M.J. Woch G. McCall M.A. Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa.Invest. Ophthalmol. Vis. Sci. 2003; 44: 1686-1695Crossref PubMed Scopus (84) Google Scholar) apparently survive longer than mouse cell suspensions (Mandai et al., 2012; West et al., 2010), and a fetal retinal graft sheet in a clinical trial was observed to survive 3 years after the transplantation, while transplants in the form of microaggregates were no longer detected (del Cerro et al., 2000).” Finally, in the same paragraph, we would like to add the following underlined words to specify graft source: “Reconstruction of a structured ONL would definitely be ideal in these cases, but it has not been clearly demonstrated that an ES/iPS-derived structured, retina-like sheet can restore visual function.” The corrected article is now online. We apologize for any confusion this may have caused or grievance to authors whose work was not cited. iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration MiceMandai et al.Stem Cell ReportsJanuary 10, 2017In BriefIn this article, Mandai and colleagues showed that iPSC retina could develop organized photoreceptor layers in the end-stage degeneration retina (rd1) after transplantation with visualized contact with host retinal cells. These transplanted mice showed light-responsive behaviors, and light responses were recorded from the host retina and host retinal ganglion cells that send output signals to the brain. Full-Text PDF Open Access