Effects of neuroactive agents on axonal growth and pathfinding of retinal ganglion cells generated from human stem cells

Effects of neuroactive agents on axonal growth and pathfinding of retinal ganglion cells... We recently established a novel method for generating functional human retinal ganglion cells (RGCs) from human induced pluripotent cells (hiPSCs). Here, we confirmed that RGCs can also be generated from human embryonic stem cells (hESCs). We investigated the usefulness of human RGCs with long axons for assessing the effects of chemical agents, such as the neurotrophic factor, nerve growth factor (NGF), and the chemorepellent factors, semaphorin 3 A (SEMA3A) and SLIT1. The effects of direct and local administration of each agent on axonal projection were evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and real-time imaging, in which the filopodia of the growth cone served as an excellent marker. A locally sustained agent system showed that the axons elongate towards NGF, but were repelled by SEMA3A and SLIT1. Focally transplanted beads that released SLIT1 bent the pathfinding of axons, imitating normal retinal development. Our innovative system for assessing the effects of chemical compounds using human RGCs may facilitate development of novel drugs for the examination, prophylaxis, and treatment of diseases. It may also be useful for observing the physiology of the optic nerve in vitro, which might lead to significant progress in the science of human RGCs. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Scientific Reports Springer Journals

Effects of neuroactive agents on axonal growth and pathfinding of retinal ganglion cells generated from human stem cells

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Publisher
Nature Publishing Group UK
Copyright
Copyright © 2017 by The Author(s)
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
eISSN
2045-2322
D.O.I.
10.1038/s41598-017-16727-1
Publisher site
See Article on Publisher Site

Abstract

We recently established a novel method for generating functional human retinal ganglion cells (RGCs) from human induced pluripotent cells (hiPSCs). Here, we confirmed that RGCs can also be generated from human embryonic stem cells (hESCs). We investigated the usefulness of human RGCs with long axons for assessing the effects of chemical agents, such as the neurotrophic factor, nerve growth factor (NGF), and the chemorepellent factors, semaphorin 3 A (SEMA3A) and SLIT1. The effects of direct and local administration of each agent on axonal projection were evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and real-time imaging, in which the filopodia of the growth cone served as an excellent marker. A locally sustained agent system showed that the axons elongate towards NGF, but were repelled by SEMA3A and SLIT1. Focally transplanted beads that released SLIT1 bent the pathfinding of axons, imitating normal retinal development. Our innovative system for assessing the effects of chemical compounds using human RGCs may facilitate development of novel drugs for the examination, prophylaxis, and treatment of diseases. It may also be useful for observing the physiology of the optic nerve in vitro, which might lead to significant progress in the science of human RGCs.

Journal

Scientific ReportsSpringer Journals

Published: Dec 1, 2017

References

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