小柯机器人

近日，美国罗彻斯特大学Ruchira Singh及其课题组利用视网膜色素上皮-脉络膜毛细血管复合物的3D iPSC模型发现与黄斑变性病理相关的因素 。相关论文于2021年3月29日在线发表在《细胞—干细胞》杂志上。

研究人员表示，眼睛中的视网膜色素上皮（RPE）-脉络膜毛细血管（CC）复合物在年龄相关性黄斑变性（AMD）和相关性黄斑营养不良（MD）中受到损害，但是可以研究AMD/MD病理生理的RPE-CC复合物体外模型仍缺乏。

通过将iPSC来源的细胞整合到基于水凝胶的细胞外基质中，研究人员开发了3D RPE-CC模型，该模型概括了健康和AMD/MD眼睛的关键特征，并提供了对RPE和CC层的模块化控制。使用此3D RPE-CC模型，研究人员证明RPE和间充质分泌因子对于形成有窗孔的CC样脉管系统都是必需的。

这些数据显示，脉络膜新血管形成（CNV）和CC萎缩能够在没有内皮细胞功能障碍的情况下发生，并且不一定继发于RPE细胞下方的玻璃疣沉积物，此外，CC萎缩和/或CNV可以由患者血清全身性启动或由突变体局部启动RPE分泌因子。最后，研究人员将FGF2和基质金属蛋白酶确定为AMD/MD的潜在治疗靶标。

附：英文原文

Title: 3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration

Author: Kannan V. Manian, Chad A. Galloway, Sonal Dalvi, Anthony A. Emanuel, Jared A. Mereness, Whitney Black, Lauren Winschel, Celia Soto, Yiming Li, Yuanhui Song, William DeMaria, Akhilesh Kumar, Igor Slukvin, Michael P. Schwartz, William L. Murphy, Bela Anand-Apte, Mina Chung, Danielle S.W. Benoit, Ruchira Singh

Issue&Volume: 2021-03-29

Abstract: The retinal pigment epithelium (RPE)-choriocapillaris (CC) complex in the eye is compromisedin age-related macular degeneration (AMD) and related macular dystrophies (MDs), yetin vitro models of RPE-CC complex that enable investigation of AMD/MD pathophysiology arelacking. By incorporating iPSC-derived cells into a hydrogel-based extracellular matrix,we developed a 3D RPE-CC model that recapitulates key features of both healthy andAMD/MD eyes and provides modular control over RPE and CC layers. Using this 3D RPE-CCmodel, we demonstrated that both RPE- and mesenchyme-secreted factors are necessaryfor the formation of fenestrated CC-like vasculature. Our data show that choroidalneovascularization (CNV) and CC atrophy occur in the absence of endothelial cell dysfunctionand are not necessarily secondary to drusen deposits underneath RPE cells, and CCatrophy and/or CNV can be initiated systemically by patient serum or locally by mutantRPE-secreted factors. Finally, we identify FGF2 and matrix metalloproteinases as potentialtherapeutic targets for AMD/MDs.

DOI: 10.1016/j.stem.2021.02.006

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00056-4

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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