Sheets of human retinal progenitor transplants improve vision in rats with severe retinal degeneration.
Sheets of human retinal progenitor transplants improve vision in rats with severe retinal degeneration.
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DOI：
10.1016/j.exer.2018.05.017
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发表时间：
2018-09
影响因子：
3.4
通讯作者：
Seiler MJ
中科院分区：
文献类型：
--
作者：
Lin B;McLelland BT;Mathur A;Aramant RB;Seiler MJ
光感受器和其他视网膜细胞的丧失是导致失明的视网膜变性（RD）疾病的常见终点。视网膜移植是一种潜在的治疗方法，以取代受损的视网膜细胞和改善视力。在这项研究中，我们研究了人类胎儿视网膜片的发展，或没有他们的视网膜色素上皮细胞（RPE）移植到免疫缺陷视网膜变性rho S334 ter-3大鼠。从胎儿人眼（妊娠11-15.7周）解剖薄片，然后移植到24-31日龄RD裸大鼠的视网膜下腔。术后每个月，通过高分辨率谱域光学相干断层扫描（SD-OCT）对眼睛进行成像。SD-OCT显示，移植物被放置到视网膜下腔中并形成分层区域或视网膜，在术后3个月在OCT中首次观察到丛状层的清晰发育。几个月后，正如预期的那样，与大鼠细胞相比，人类细胞的发育要慢得多，移植的光感受器发育出了内节和外节。通过免疫组织化学分析视网膜切片中的人类和视网膜标记物，并证实视网膜层内形成了几种视网膜亚型。移植细胞延长了突起，也可以看到许多细胞迁移到宿主视网膜。在术后5.8 - 8.6个月，将选定的大鼠暴露于闪光并记录上级丘（中脑的视觉中心）的视觉反应。7只移植的大鼠中有4只在上级丘的有限区域对闪光有反应。在年龄匹配的RD对照（非手术或假手术）中，未发现相同昏暗光强度的反应。总之，我们的数据表明，人胎视网膜片移植到严重紊乱的RD裸大鼠视网膜下腔发育成熟的光感受器和其他视网膜细胞，与宿主整合，并诱导视力改善。
Loss of photoreceptors and other retinal cells is a common endpoint in retinal degenerate (RD) diseases that cause blindness. Retinal transplantation is a potential therapy to replace damaged retinal cells and improve vision. In this study, we examined the development of human fetal retinal sheets with or without their retinal pigment epithelium (RPE) transplanted to immunodeficient retinal degenerate rho S334ter-3 rats. Sheets were dissected from fetal human eyes (11–15.7 weeks gestation) and then transplanted to the subretinal space of 24–31 d old RD nude rats. Every month post surgery, eyes were imaged by high-resolution spectral-domain optical coherence tomography (SD-OCT). SD-OCT showed that transplants were placed into the subretinal space and developed laminated areas or rosettes, with clear development of plexiform layers first seen in OCT at 3 months post surgery. Several months later, as could be expected by the much slower development of human cells compared to rat cells, transplant photoreceptors developed inner and later outer segments. Retinal sections were analyzed by immunohistochemistry for human and retinal markers and confirmed the formation of several retinal subtypes within the retinal layers. Transplant cells extended processes and a lot of the cells could also be seen migrating into the host retina. At 5.8 – 8.6 months post surgery, selected rats were exposed to light flashes and recorded for visual responses in superior colliculus, (visual center in midbrain). Four of seven rats with transplants showed responses to flashes of light in a limited area of superior colliculus. No response with the same dim light intensity was found in age-matched RD controls (non-surgery or sham surgery). In summary, our data showed that human fetal retinal sheets transplanted to the severely disturbed subretinal space of RD nude rats develop mature photoreceptors and other retinal cells, integrate with the host and induce vision improvement.
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影响因子：
5.9
作者：
Assawachananont, Juthaporn;Mandai, Michiko;Okamoto, Satoshi;Yamada, Chikako;Eiraku, Mototsugu;Yonemura, Shigenobu;Sasai, Yoshiki;Takahashi, Masayo
通讯作者：
Takahashi, Masayo
影响因子：
5.9
作者：
Iraha S;Tu HY;Yamasaki S;Kagawa T;Goto M;Takahashi R;Watanabe T;Sugita S;Yonemura S;Sunagawa GA;Matsuyama T;Fujii M;Kuwahara A;Kishino A;Koide N;Eiraku M;Tanihara H;Takahashi M;Mandai M
通讯作者：
Mandai M
DOI：
10.1007/s004170050169
发表时间：
1998-11-01
影响因子：
2.7
作者：
Ivert, L;Gouras, P;Narfstrom, K
通讯作者：
Narfstrom, K
DOI：
10.1136/bjophthalmol-2015-306972
发表时间：
2016-01
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Hanus J;Zhao F;Wang S
通讯作者：
Wang S
影响因子：
2.3
作者：
Cooper, Ann E.;Cho, Jang-Hyeon;Klassen, Henry
通讯作者：
Klassen, Henry