Prof. Larry Benowitz: the future of optic nerve regeneration and the difficulty of keeping retinal ganglion cells alive

2018 ◽  
Vol 3 ◽  
pp. 30-30
Author(s):  
Wei-En Fan
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Optic Nerve Regeneration ◽  
The Future

scholarly journals Knocking Out Non-muscle Myosin II in Retinal Ganglion Cells Promotes Long-Distance Optic Nerve Regeneration

Cell Reports ◽  
2020 ◽  
Vol 31 (3) ◽  
pp. 107537 ◽  
Author(s):  
Xue-Wei Wang ◽  
Shu-Guang Yang ◽  
Chi Zhang ◽  
Ming-Wen Hu ◽  
Jiang Qian ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Myosin Ii ◽  
Retinal Ganglion ◽  
Long Distance ◽  
Optic Nerve Regeneration ◽  
Muscle Myosin

scholarly journals Upregulation of IGF-I in the goldfish retinal ganglion cells during the early stage of optic nerve regeneration

2007 ◽  
Vol 50 (5) ◽  
pp. 749-756 ◽  
Author(s):  
Yoshiki Koriyama ◽  
Keiko Homma ◽  
Kayo Sugitani ◽  
Yoshihiro Higuchi ◽  
Toru Matsukawa ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Early Stage ◽  
Retinal Ganglion ◽  
Optic Nerve Regeneration ◽  
Igf I

scholarly journals Chemokine CCL5 promotes robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy

2021 ◽  
Vol 118 (9) ◽  
pp. e2017282118 ◽  
Author(s):  
Lili Xie ◽  
Yuqin Yin ◽  
Larry Benowitz
Keyword(s):  
Gene Therapy ◽  
Optic Nerve ◽  
Nerve Regeneration ◽  
Viral Vectors ◽  
Ganglion Cells ◽  
Projection Neurons ◽  
Retinal Ganglion ◽  
Optic Nerve Regeneration ◽  
Beneficial Effects ◽  
Chemokine Ligand

Ciliary neurotrophic factor (CNTF) is a leading therapeutic candidate for several ocular diseases and induces optic nerve regeneration in animal models. Paradoxically, however, although CNTF gene therapy promotes extensive regeneration, recombinant CNTF (rCNTF) has little effect. Because intraocular viral vectors induce inflammation, and because CNTF is an immune modulator, we investigated whether CNTF gene therapy acts indirectly through other immune mediators. The beneficial effects of CNTF gene therapy remained unchanged after deleting CNTF receptor alpha (CNTFRα) in retinal ganglion cells (RGCs), the projection neurons of the retina, but were diminished by depleting neutrophils or by genetically suppressing monocyte infiltration. CNTF gene therapy increased expression of C-C motif chemokine ligand 5 (CCL5) in immune cells and retinal glia, and recombinant CCL5 induced extensive axon regeneration. Conversely, CRISPR-mediated knockdown of the cognate receptor (CCR5) in RGCs or treating wild-type mice with a CCR5 antagonist repressed the effects of CNTF gene therapy. Thus, CCL5 is a previously unrecognized, potent activator of optic nerve regeneration and mediates many of the effects of CNTF gene therapy.

scholarly journals Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration

2019 ◽  
Author(s):  
Xue-Wei Wang ◽  
Shu-Guang Yang ◽  
Chi Zhang ◽  
Jin-Jin Ma ◽  
Yingchi Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Axon Regeneration ◽  
Ganglion Cells ◽  
Myosin Ii ◽  
Retinal Ganglion ◽  
Long Distance ◽  
Optic Nerve Regeneration ◽  
Cytoskeletal Dynamics

AbstractIn 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 showed that knocking out myosin IIA/B in retinal ganglion cells alone either before or after optic nerve crush induced marked and sustained optic nerve regeneration. Combined Lin28 overexpression and myosin IIA/B knockout led to synergistic promoting effect and long-distance axon regeneration. Immunostaining, RNA-seq and western blot analyses revealed that myosin II deletion did not affect known axon regeneration signaling pathways or the expression of regeneration associated genes. Instead, it abolished the retraction bulb formation and significantly enhanced the axon extension efficiency. The study provided clear evidence that directly targeting neuronal cytoskeleton was sufficient to induce strong CNS axon regeneration, and combining gene expression in the soma and modified cytoskeletal dynamics in the axon was a promising approach for long-distance CNS axon regeneration.

Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells

2019 ◽  
Vol 25 (28) ◽  
pp. 3057-3073 ◽  
Author(s):  
Kobra B. Juybari ◽  
Azam Hosseinzadeh ◽  
Habib Ghaznavi ◽  
Mahboobeh Kamali ◽  
Ahad Sedaghat ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Nerve Fibers ◽  
Retinal Ganglion

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

scholarly journals Translational profiling of retinal ganglion cell optic nerve regeneration in Xenopus laevis

2017 ◽  
Vol 426 (2) ◽  
pp. 360-373 ◽  
Author(s):  
G.B. Whitworth ◽  
B.C. Misaghi ◽  
D.M. Rosenthal ◽  
E.A. Mills ◽  
D.J. Heinen ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Xenopus Laevis ◽  
Ganglion Cell ◽  
Nerve Regeneration ◽  
Retinal Ganglion Cell ◽  
Retinal Ganglion ◽  
Optic Nerve Regeneration
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