Knocking Out Non-muscle Myosin II in Retinal Ganglion Cells Promotes Long-Distance Optic Nerve Regeneration
Xue-Wei Wang,
Shu-Guang Yang,
Chi Zhang,
Ming-Wen Hu,
Jiang Qian,
Jin-Jin Ma,
Yingchi Zhang,
Bin-Bin Yang,
Yi-Lan Weng,
Guo-Li Ming,
Anish R. Kosanam,
Saijilafu,
Feng-Quan Zhou
Affiliations
Xue-Wei Wang
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Shu-Guang Yang
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Chi Zhang
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Ming-Wen Hu
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Jiang Qian
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Jin-Jin Ma
Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu 215007, China
Yingchi Zhang
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Bin-Bin Yang
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Yi-Lan Weng
Center for Neuroregeneration, Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX 77030, USA
Guo-Li Ming
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Anish R. Kosanam
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Saijilafu
Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu 215007, China; Department of Orthopaedic Surgery, the First Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215007, China; Corresponding author
Feng-Quan Zhou
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
Summary: In addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here, we show that knocking out myosin IIA and IIB (myosin IIA/B) in retinal ganglion cells alone, either before or after optic nerve crush, induces significant optic nerve regeneration. Combined Lin28a overexpression and myosin IIA/B knockout lead to an additive promoting effect and long-distance axon regeneration. Immunostaining, RNA sequencing, and western blot analyses reveal that myosin II deletion does not affect known axon regeneration signaling pathways or the expression of regeneration-associated genes. Instead, it abolishes the retraction bulb formation and significantly enhances the axon extension efficiency. The study provides clear evidence that directly targeting neuronal cytoskeleton is sufficient to induce significant CNS axon regeneration and that combining altered gene expression in the soma and modified cytoskeletal dynamics in the axon is a promising approach for long-distance CNS axon regeneration. : Although modulating the neuronal cytoskeleton has been deemed a promising approach to enhance mammalian axon regeneration, only a few studies have shown convincing results, especially in the central nervous system. Wang et al. demonstrate that the deletion of non-muscle myosin II sufficiently induces significant mammalian CNS axon regeneration in vivo. Keywords: axon regeneration, optic nerve regeneration, non-muscle myosin II, retinal ganglion cells, Lin28, growth cone, retraction bulb, cytoskeleton, post-injury treatment
