期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 109, 期 2, 页码 168-173出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.08R19FM
关键词
neurogenesis; rod and cone photoreceptor; eye; cell replacement; induced pluripotent stem (iPS) cell; glycogen synthase kinase-3 beta (GSK-3 beta)
资金
- MEXT
- Leading Project
- Japan Society for the Promotion of Science
- Mochida Memorial Foundation
Recent advances in stern cell biology have provided new insights that may lead to the development of regeneration therapy in the central nervous system to replenish lost neurons and to reconstitute neural circuits. The strategies for regeneration can be classified into two approaches: 1) activation of endogenous neural stem cells and ii) transplantation of donor cells to replace lost cells. In the adult mammalian retina, Muller glia generate new retinal neurons in response to injury. The proliferation and differentiation of Muller glia-derived progenitors can be controlled by both intrinsic and extrinsic factors. Members of the Wnt/beta-catenin signaling pathway, such as Writ receptors and glycogen synthase kinase-3 beta, may be promising drug targets for neural regeneration. On the other hand, transplantation of photoreceptors or retinal pigment epithelia derived from human embryonic stem cells or induced pluripotent stem cells is also promising. Directed differentiation of pluripotent cells into retinal cells and purification to obtain retinal cells at a specific ontogenetic stage are required for donor cell preparation. Modulation of the host retinal environment to reduce the glial barrier is also critical for transplantation. To restore visual function, we need to understand the mechanisms underlying the integration of newly generated neurons or transplanted cells into the existing neural networks.
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