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自体诱导多能干细胞来源的视网膜色素上皮细胞移植治疗渗出性年龄相关性黄斑变性的评估

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

作者信息

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

机构信息

Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Teikyo University, University Hospital Mizonokuchi, Kanagawa, Japan.

Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Kobe, Japan.

出版信息

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

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

摘要

目的

报告首例诱导多能干细胞(iPSC)来源的视网膜色素上皮(RPE)片自体移植4年的随访结果,此前曾对该病例进行过介绍,并采用了多模态成像技术。

设计

单病例随访。

研究对象

一名患有渗出性年龄相关性黄斑变性和息肉状脉络膜血管病变的患者。

方法

2014年9月在切除脉络膜新生血管(CNV)后,移植自体iPSC来源的RPE细胞片。

主要观察指标

术后4年通过彩色眼底照相、光谱域(SD)光学相干断层扫描(OCT)、荧光素血管造影、吲哚菁绿血管造影和自适应光学(AO)视网膜相机评估移植物的功能。

结果

在4年随访时,移植的自体iPSC来源的RPE片在视网膜下存活,色素沉着区域略有扩大,未出现不良事件。移植物上方和相邻的外核层厚度可接受,结构有序。荧光素血管造影和SD OCT显示,在与术前息肉状脉络膜血管病变残留主干血管相关的移植区域内存在血管样结构,但无渗出性改变。视力稳定,无需额外注射抗血管内皮生长因子药物。与切除CNV后无RPE的该部位以外的体积相比,移植部位的脉络膜体积相对保留。吲哚菁绿血管造影显示iPSC来源的RPE片周围的脉络膜毛细血管得以保留。通过AO成像在移植物片边缘附近区域观察到主要呈六边形排列的暗细胞样结构。发现细胞间平均距离随时间稳定。

结论

迄今为止,移植的iPSC来源的RPE片已存活4年,似乎支持光感受器和脉络膜血管。在移植部位观察到了RPE的形态学特征。

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