Partially Differentiated Neuroretinal Cells Promote Maturation of the Retinal Pigment Epithelium.

Partially Differentiated Neuroretinal Cells Promote Maturation of the Retinal Pigment Epithelium.
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DOI:
10.1167/iovs.61.13.9
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发表时间:
2020-11-02
影响因子:
4.4
通讯作者:
Rizzolo LJ
Rizzolo LJ
中科院分区:
医学2区
文献类型:
--
作者:
Singh D;Chen X;Xia T;Ghiassi-Nejad M;Tainsh L;Adelman RA;Rizzolo LJ

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许多研究已经证明视网膜色素上皮 (RPE) 能够促进视网膜发育成熟。很少有研究探讨视网膜发育对 RPE 的相互影响。从人类胎儿 RPE 中分离出来的 RPE 或从人类干细胞中分化出来的 RPE 在 Transwell 滤芯上进行培养。视网膜祖细胞 (RPC) 由人类干细胞分化而来,并培养在由明胶、硫酸软骨素、透明质酸和层粘连蛋白-521 组成的平面支架上。通过定量 RT-PCR、免疫荧光、免疫印迹和跨上皮电阻 (TER) 分析培养物。 RPC最初分化成几种类似视网膜的细胞类型,这些细胞类型彼此分离并形成松散组织的层或区域。随着时间的推移,假定的光感受器和神经节细胞层持续存在,但中间区域以表达神经胶质标记物的细胞为主,没有双极细胞或中间神经元的证据。这种不发达的类视黄醇与 RPE 的共培养导致恢复蛋白阳性细胞层增厚,但并不能阻止中间区域中神经元标记的丢失。尽管没有观察到光感受器内节和外节,但免疫印迹显示共培养增加了视紫红质和红/绿视蛋白的表达。 RPE 与这种不发达的视网膜培养物的共培养增加了 RPE 的 TER 和 RPE 特征基因的表达。这些研究表明,不成熟的感觉神经视网膜可以促进 RPE 的成熟;然而,RPE 单独促进神经感觉视网膜成熟的能力是有限的。
Many studies have demonstrated the ability of the retinal pigment epithelium (RPE) to foster the maturation of the developing retina. Few studies have examined the reciprocal effects of developing retina on the RPE. RPE isolated from human fetal RPE or differentiated from human stem cells was cultured on Transwell filter inserts. Retinal progenitor cells (RPCs) were differentiated from human stem cells and cultured on a planar scaffold composed of gelatin, chondroitin sulfate, hyaluronic acid, and laminin-521. Cultures were analyzed by quantitative RT-PCR, immunofluorescence, immunoblotting, and transepithelial electrical resistance (TER). RPCs initially differentiated into several retina-like cell types that segregated from one another and formed loosely organized layers or zones. With time, the presumptive photoreceptor and ganglion cell layers persisted, but the intervening zone became dominated by cells that expressed glial markers with no evidence of bipolar cells or interneurons. Co-culture of this underdeveloped retinoid with the RPE resulted in a thickened layer of recoverin-positive cells but did not prevent the loss of interneuron markers in the intervening zone. Although photoreceptor inner and outer segments were not observed, immunoblots revealed that co-culture increased expression of rhodopsin and red/green opsin. Co-culture of the RPE with this underdeveloped retinal culture increased the TER of the RPE and the expression of RPE signature genes. These studies indicated that an immature neurosensory retina can foster maturation of the RPE; however, the ability of RPE alone to foster maturation of the neurosensory retina is limited.
人类诱导的多能干细胞产生具有可变和养分依赖性效率的光响应性视网膜器官。
DOI: 10.1002/stem.2883
发表时间: 2018-10
期刊: Stem cells (Dayton, Ohio)
影响因子: --
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DOI: 10.1167/iovs.10-6440
发表时间: 2011-07-01
影响因子: 4.4
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发表时间: 1997-11-14
期刊: CELL
影响因子: 64.5
作者:
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