scholarly journals Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve

2016 ◽  
Vol 2 ◽  
pp. 205521731664170 ◽  
Author(s):  
Melissa M Gresle ◽  
Yaou Liu ◽  
Trevor J Kilpatrick ◽  
Dennis Kemper ◽  
Qi-Zhu Wu ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Axonal Regeneration ◽  
Antibody Therapy ◽  
Experimental Models ◽  
Therapeutic Effects ◽  
Axonal Loss ◽  
Nerve Crush ◽  
Acute Optic Neuritis ◽  
Injury Models

Background Two ongoing phase II clinical trials (RENEW and SYNERGY) have been developed to test the efficacy of anti-LINGO-1 antibodies in acute optic neuritis and relapsing forms of multiple sclerosis, respectively. Across a range of experimental models, LINGO-1 has been found to inhibit neuron and oligodendrocyte survival, axon regeneration, and (re)myelination. The therapeutic effects of anti-LINGO-1 antibodies on optic nerve axonal loss and regeneration have not yet been investigated. Objective In this series of studies we investigate if LINGO-1 antibodies can prevent acute inflammatory axonal loss, and promote axonal regeneration after injury in rodent optic nerves. Methods The effects of anti-LINGO-1 antibody on optic nerve axonal damage were assessed using rodent myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (EAE), and its effects on axonal regeneration were assessed in optic nerve crush injury models. Results In the optic nerve, anti-LINGO-1 antibody therapy was associated with improved optic nerve parallel diffusivity measures on MRI in mice with EAE and reduced axonal loss in rat EAE. Both anti-LINGO-1 antibody therapy and the genetic deletion of LINGO-1 reduced nerve crush-induced axonal degeneration and enhanced axonal regeneration. Conclusion These data demonstrate that LINGO-1 blockade is associated with axonal protection and regeneration in the injured optic nerve.

Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway

2012 ◽  
Vol 63 (6) ◽  
pp. 1182-1190 ◽  
Author(s):  
Haibo Tan ◽  
Yisheng Zhong ◽  
Xi Shen ◽  
Yu Cheng ◽  
Qin Jiao ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Signaling Pathway ◽  
Axonal Regeneration ◽  
Optic Nerve Crush ◽  
Nerve Crush

scholarly journals The Angiotensin II Type 2 (AT2) Receptor Promotes Axonal Regeneration in the Optic Nerve of Adult Rats

1998 ◽  
Vol 188 (4) ◽  
pp. 661-670 ◽  
Author(s):  
Ralph Lucius ◽  
Stefan Gallinat ◽  
Philip Rosenstiel ◽  
Thomas Herdegen ◽  
Jobst Sievers ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Receptor Antagonist ◽  
Axonal Regeneration ◽  
At1 Receptor ◽  
At2 Receptor ◽  
Ang Ii ◽  
Adult Rats ◽  
Nerve Crush ◽  
Retinal Explants

The renin-angiotensin system (RAS) has been traditionally linked to blood pressure and volume regulation mediated through the angiotensin II (ANG II) type 1 (AT1) receptor. Here we report that ANG II via its ANG II type 2 (AT2) receptor promotes the axonal elongation of postnatal rat retinal explants (postnatal day 11) and dorsal root ganglia neurons in vitro, and, moreover, axonal regeneration of retinal ganglion cells after optic nerve crush in vivo. In retinal explants, ANG II (10−7–10−5 M) induced neurite elongation via its AT2 receptor, since the effects were mimicked by the AT2 receptor agonist CGP 42112 (10−5 M) and were entirely abolished by costimulation with the AT2 receptor antagonist PD 123177 (10−5 M), but not by the AT1 receptor antagonist losartan (10−5 M). To investigate whether ANG II is able to promote axonal regeneration in vivo, we performed optic nerve crush experiments in the adult rats. After ANG II treatment (0.6 nmol), an increased number of growth-associated protein (GAP)-43–positive fibers was detected and the regenerating fibers regularly crossed the lesion site (1.6 mm). Cotreatment with the AT2 receptor antagonist PD 123177 (6 nmol), but not with the AT1 receptor antagonist losartan (6 nmol), completely abolished the ANG II–induced axonal regeneration, providing for the first time direct evidence for receptor-specific neurotrophic action of ANG II in the central nervous system of adult mammals and revealing a hitherto unknown function of the RAS.

Axon Regeneration in the Mammalian Optic Nerve

2020 ◽  
Vol 6 (1) ◽  
pp. 195-213
Author(s):  
Philip R. Williams ◽  
Larry I. Benowitz ◽  
Jeffrey L. Goldberg ◽  
Zhigang He
Keyword(s):  
Optic Nerve ◽  
Ganglion Cells ◽  
Traumatic Injury ◽  
Optic Glioma ◽  
Retinal Ganglion ◽  
Degenerative Diseases ◽  
Nerve Crush ◽  
Neural Repair ◽  
Molecular Logic ◽  
Injury Models

The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.

scholarly journals Experimental Models of Glaucoma

2022 ◽  
Vol 14 (4) ◽  
pp. 164-171
Author(s):  
O. N. Onufriichuk ◽  
I. R. Gazizova ◽  
A. V. Kuroyedov ◽  
А. V. Seleznev ◽  
A. Yu. Brezhnev
Keyword(s):  
Optic Nerve ◽  
Optic Disc ◽  
Experimental Models ◽  
Diagnostic Methods ◽  
Trophic Factors ◽  
Processing Technologies ◽  
Functional Changes ◽  
Non Invasive ◽  
Digital Scanning

Optic nerve pits are a mono- or bilateral congenital anomaly represented by optic disc depressions of various sizes. In half of the cases, the pits are complicated by edema, central retinal detachment and retinoschisis, and cause visual function decrease. Visual acuity losses can be either insignificant or pronounced. Optic discs pits have been investigated massively over the last century and a half, but their etiology is still underresearched. In recent years, however, due to the development of digital scanning and data processing technologies and the emergence of non-invasive highly informative diagnostic methods, it has become possible to reveal structural and functional changes of the optic disc in vivo, in addition to the traditional detection of histological changes in cadaveric eyes.Glaucomatous process modeling is one of the challenges in ophthalmology. And this is due primarily to the fact that, so far, the main reasons for the onset and progression of glaucoma. Numerous works on experimental research in its core model ocular. However, there are forms of glaucoma, which are independent of the level of intraocular pressure. Ideal model of glaucoma is considered a model with the development of the characteristic symptom in which a key symptom is a slowly progressive excavation of the optic nerve. But given the new knowledge in the pathogenesis of neurodegenerative changes in glaucoma in this model should be added and the opportunity to study the brain, vascular factors of progression, the level of neurotransmitters, trophic factors, etc. Therefore, we tried to make the analysis of models of glaucoma in various experimental animals and determine the most appropriate model for studying the pathogenesis of glaucoma.

Microvesicles from Schwann-Like Cells as a New Biomaterial Promote Axonal Growth

2021 ◽  
Vol 17 (2) ◽  
pp. 291-302
Author(s):  
Kai Ye ◽  
Jiahong Yu ◽  
Li Li ◽  
Hui Wang ◽  
Bin Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Schwann Cells ◽  
Axonal Regeneration ◽  
Embryonic Stem ◽  
Axonal Growth ◽  
Nerve Tissue ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Dorsal Root Ganglia Neurons

Schwann cells promote axonal regeneration following peripheral nerve injury. However, in terms of clinical treatment, the therapeutic effects of Schwann cells are limited by their source. The transmission of microvesicles from neuroglia cells to axons is a novel communication mechanism in axon regeneration.To evaluate the effect of microvesicles released from Schwann-like cells on axonal regeneration, neural stem cells derived from human embryonic stem cells differentiated into Schwann-like cells, which presented a typical morphology and characteristics similar to those of schwann cells. The glial markers like MBP, P0, P75NTR, PMP-22, GFAP, HNK-1 and S100 were upregulated, whereas the neural stem markers like NESTIN, SOX1 and SOX2 were significantly downregulated in schwann-like cells. Microvesicles enhanced axonal growth in dorsal root ganglia neurons and regulated GAP43 expression in neuron-like cells (N2A and PC12) through the PTEN/PI3 K/Akt signaling pathway. A 5 mm section of sciatic nerve was transected in Sprague-Dawley rats. With microvesicles transplantation, regenerative nerves were evaluated after 6 weeks. Microvesicles increased sciatic function index scores, delayed gastrocnemius muscle atrophy and elevated βIII-tubulin-labeled axons in vivo. Schwann-like cells serve as a convenient source and promote axonal growth by secreting microvesicles, which may potentially be used as bioengineering materials for nerve tissue repair.

Changes in retinal ganglion cell axons after optic nerve crush: neurofilament expression is not the sole determinant of calibre

1995 ◽  
Vol 73 (9-10) ◽  
pp. 599-604 ◽  
Author(s):  
Michael Minzenberg ◽  
Michelle Berkelaar ◽  
Garth Bray ◽  
Lisa Mckerracher
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Time Course ◽  
Intact Cell ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Axonal Loss ◽  
Retinal Ganglion ◽  
Nerve Crush

After injury in the central nervous system of adult mammals, many of the axons that remain attached to their intact cell bodies degenerate and decrease in calibre. To understand this process better, we have investigated the relationship between axonal loss, cell loss, and the time course of changes in axonal calibre. Optic nerves (ONs) were crushed and the numbers and sizes of axons remaining close to the cell bodies (2 mm from the eye) and near the site of the lesion (6 mm from the eye) were determined for nerves examined between 1 week and 3 months after injury. Comparison with the retinal ganglion cell (RGC) counts from the same animals revealed that axonal loss was concomitant with cell body loss for at least the first 2 weeks after injury. However, there was no significant change in the calibre of the surviving neurons until 1 month after injury. Thereafter, the axonal calibre was decreased equally along the ON. No progressive somatofugal atrophy was observed. These decreases in axonal calibre occur much later than the immediate drop in neurofilament (NF) expression that also follows injury. The late effect of injury on axonal calibre suggests that NF expression is not the sole determinant of axon size of the RGC fibers in the ON. Other factors are likely additional contributing factors, such as the decreased rate of axonal transport that would help maintain the axonal neurofilament content.Key words: axonal calibre, axotomy, neuronal cell death, neurofilaments, retinal ganglion cell, optic nerve.

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