Evaluation of Transplanted Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in Exudative Age-Related Macular Degeneration

Seiji Takagi; Michiko Mandai; Kiyoko Gocho; Yasuhiko Hirami; Midori Yamamoto; Masashi Fujihara; Sunao Sugita; Yasuo Kurimoto; Masayo Takahashi

doi:10.1016/j.oret.2019.04.021

Evaluation of Transplanted Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in Exudative Age-Related Macular Degeneration

Ophthalmol Retina. 2019 Oct;3(10):850-859. doi: 10.1016/j.oret.2019.04.021. Epub 2019 Apr 26.

Authors

Seiji Takagi¹, Michiko Mandai², Kiyoko Gocho³, Yasuhiko Hirami⁴, Midori Yamamoto⁵, Masashi Fujihara⁶, Sunao Sugita⁷, Yasuo Kurimoto⁴, Masayo Takahashi⁷

Affiliations

¹ Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Teikyo University, University Hospital Mizonokuchi, Kanagawa, Japan.
² Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Kobe, Japan. Electronic address: michiko.mandai@riken.jp.
³ Department of Ophthalmology, Nippon Medical School, Chiba Hokuso Hospital, Chiba, Japan.
⁴ Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan.
⁵ Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan.
⁶ Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan.
⁷ Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Kobe, Japan.

PMID: 31248784
DOI: 10.1016/j.oret.2019.04.021

Abstract

Purpose: To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet autologous transplantation using multimodal imaging.

Design: Follow-up of a single case.

Participant: A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy.

Methods: Transplantation of an autologous iPSC-derived RPE cell sheet after removal of choroidal neovascularization (CNV) in September 2014.

Main outcome measures: The function of the graft was assessed 4 years after surgery by color fundus photography, spectral-domain (SD) OCT, fluorescein angiography, indocyanine green angiography, and an adaptive optics (AO) retinal camera.

Results: At the 4-year follow-up, the transplanted autologous iPSC-derived RPE sheet had survived beneath the retina with slight expansion of the pigmented area and no adverse events. The outer nuclear layer above and adjacent to the graft showed acceptable thickness and an organized structure. Fluorescein angiography and SD OCT suggested the presence of vessel-like structures confined to the grafted area associated with the remaining trunk vessel of preoperative polypoidal choroidal vasculopathy but with no exudative changes. Visual acuity has been stable with no additional injections of anti-vascular endothelial growth factor agent. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the CNV. Indocyanine green angiography revealed a preserved choriocapillaris around the iPSC-derived RPE sheet. Dark cell-like structures with a predominantly hexagonal arrangement were observed by AO imaging in an area located near the margin of the graft sheet. The average intercell distance was found to be stable over time.

Conclusions: Thus far, the grafted iPSC-derived RPE sheet has survived for 4 years and seems to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Female
Fluorescein Angiography / methods
Follow-Up Studies
Fundus Oculi
Humans
Ophthalmologic Surgical Procedures / methods*
Pluripotent Stem Cells / transplantation*
Retinal Pigment Epithelium / cytology
Retinal Pigment Epithelium / transplantation*
Retrospective Studies
Tomography, Optical Coherence / methods
Transplantation, Autologous
Visual Acuity*
Wet Macular Degeneration / diagnosis
Wet Macular Degeneration / surgery*