1. Effects of constitutively active K-Ras on axon regeneration after optic nerve injury.
- Author
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Kiyota N, Namekata K, Nishijima E, Guo X, Kimura A, Harada C, Nakazawa T, and Harada T
- Subjects
- Humans, Axons physiology, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-Kinases, Nerve Regeneration physiology, Optic Nerve Injuries
- Abstract
Visual disturbance after optic nerve injury is a serious problem. Attempts have been made to enhance the intrinsic ability of retinal ganglion cells (RGCs) to regenerate their axons, and the importance of PI3K/Akt and RAF/MEK/ERK signal activation has been suggested. Since these signals are shared with oncogenic signaling cascades, in this study, we focused on a constitutively active form of K-Ras, K-Ras
V12 , to determine if overexpression of this molecule could stimulate axon regeneration. We confirmed that K-RasV12 phosphorylated Akt and ERK in vitro. Intravitreal delivery of AAV2-K-RasV12 increased the number of surviving RGCs and promoted 1.0 mm of axon regeneration one week after optic nerve injury without inducing abnormal proliferative effects in the RGCs. In addition, AAV2-K-RasV12 induced robust RGC axon regeneration, reaching as far as approximately 2.5 mm from the injury site, in eight weeks. Our findings suggest that AAV2-K-RasV12 could provide a good model for speedy and efficient analysis of the mechanism underlying axon regeneration in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
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