Establishment of models for retinal regenerative medicine using the eye-like structures from ES cells

从未分化的胚胎干细胞中培养出由晶状体、神经视网膜和视网膜色素上皮(RPE)细胞组成的眼样结构的培养体系已经建立。在培养中分化的RPE细胞前体对Wnt2b信号有反应，并经回顾性鉴定形成次级集落，仅由眼部结构中的RPE样细胞组成。这些移植的眼样结构能够作为神经视网膜和RPE细胞填充发育中的鸡眼。从移植的眼状结构中长出的成熟RPE细胞的单细胞层证实了RPE细胞前体的存在。这些结果表明，眼状结构是在活体内产生眼睛的正常发育途径的结果。此外，眼样结构衍生细胞有效地再生了经NMDA处理的受损视网膜神经节细胞，包括那些延伸到视网膜乳头的轴突。如果能够确定这些细胞的功能效应，这种类似眼睛的结构可能被用来建立各种眼病的治疗模型。

A culture system to generate eye-like structures consisting of lens, neural retina, and retinal pigmented epithelium (RPE) cells from undifferentiated embryonic stem cells has been established. Precursors of RPE cells that differentiated in the cultures were responsive to Wnt2b signaling and identified retrospectively to form secondary colonies consisting of only RPE-like cells in eye-like structures. These transplanted eye-like structures were capable of populating the developing chick eye as neuronal retina and RPE cells. The outgrowth of a single cell layer of mature RPE cells from the grafted eye-like structures confirmed the existence of precursors for RPE cells. These results suggest that the eye-like structures resulted from the normal developmental pathway responsible for generating eyes in vivo. In addition, eye-like structure-derived cells efficiently regenerated injured retinal ganglion cells treated with NMDA, including those extending axons to retinal papilla. If a functional effect of these cells can be established, such eye-like structures may be potentially used to establish therapy models for various eye diseases.