Indirect traumatic optic neuropathy: modeling optic nerve injury in the context of closed head trauma

Burke, Emma G; Cansler, Shelby M.; Evanson, Nathan K.

doi:10.4103/1673-5374.247463

“…Damage to RGC and optic nerve have not been consistently studied in other mouse models of blast injury. In some models, only RGC loss was reported 34,35 , while some of the mouse models of blast injury are characterized by traumatic optic neuropathy and can be used to model indirect traumatic optic neuropathy in the context of head trauma [36][37][38] . Other models of indirect trauma-induced injury of the optic nerve use external ultrasound energy instead of an air blast 39,40 .…”

Section: Discussionmentioning

confidence: 99%

Axonopathy precedes cell death in ocular damage mediated by blast exposure

Boehme

¹

,

Hedberg-Buenz

²

,

Tatro

³

et al. 2021

Sci Rep

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Traumatic brain injuries (TBI) of varied types are common across all populations and can cause visual problems. For military personnel in combat settings, injuries from blast exposures (bTBI) are prevalent and arise from a myriad of different situations. To model these diverse conditions, we are one of several groups modeling bTBI using mice in varying ways. Here, we report a refined analysis of retinal ganglion cell (RGC) damage in male C57BL/6J mice exposed to a blast-wave in an enclosed chamber. Ganglion cell layer thickness, RGC density (BRN3A and RBPMS immunoreactivity), cellular density of ganglion cell layer (hematoxylin and eosin staining), and axon numbers (paraphenylenediamine staining) were quantified at timepoints ranging from 1 to 17-weeks. RNA sequencing was performed at 1-week and 5-weeks post-injury. Earliest indices of damage, evident by 1-week post-injury, are a loss of RGC marker expression, damage to RGC axons, and increase in glial markers expression. Blast exposure caused a loss of RGC somas and axons—with greatest loss occurring by 5-weeks post-injury. While indices of glial involvement are prominent early, they quickly subside as RGCs are lost. The finding that axonopathy precedes soma loss resembles pathology observed in mouse models of glaucoma, suggesting similar mechanisms.

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“…( Warner and Eggenberger, 2010 ; Singman et al, 2016 ) Patients with ITON can experience severe vision loss, and while some experience limited recovery, they never return to baseline. ( Singman et al, 2016 ; Burke et al, 2019 ) Corticosteroids or observation alone are the current standards of treatment for patients with ITON. ( Volpe and Levin, 2011 )…”

Section: Introductionmentioning

confidence: 99%

Galantamine protects against synaptic, axonal, and vision deficits in experimental neurotrauma

Naguib

¹

,

Bernardo-Colón

²

,

Cencer

³

et al. 2020

Neurobiology of Disease

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Our goal was to investigate the neuroprotective effects of galantamine in a mouse model of blast-induced indirect traumatic optic neuropathy (bITON). Galantamine is an FDA-approved acetylcholinesterase inhibitor used to treat mild-moderate Alzheimer’s disease. We exposed one eye of an anesthetized mouse to repeat bursts of over-pressurized air to induce traumatic optic neuropathy. Mice were given regular or galantamine-containing water (120 mg/L) ad libitum, beginning immediately after blast and continuing for one month. Electroretinograms and visual evoked potentials were performed just prior to endpoint collection. Histological and biochemical assessments were performed to assess activation of sterile inflammation, axon degeneration, and synaptic changes. Galantamine treatment mitigated visual function deficits induced by our bITON model via preservation of the b-wave of the electroretinogram and the N1 of the visual evoked potential. We also observed a reduction in axon degeneration in the optic nerve as well as decreased rod bipolar cell dendritic retraction. Galantamine also showed anti-inflammatory and antioxidant effects. Galantamine may be a promising treatment for blast-induced indirect traumatic optic neuropathy as well as other optic neuropathies.

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“…ON transection and ONC are both models of direct TON: they are considered easy to perform and directly damage the nerve by cutting or crushing [ 36 ]. Transection models produce complete injury of the ON and interruption of all axons so that it is limited in terms of studying ON protection and treatment [ 36 , 37 ]. In ONC model, injury could be either complete or incomplete, depending on the magnitude and duration of the force applied [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Astragalus membranaceus Injection Protects Retinal Ganglion Cells by Regulating the Nerve Growth Factor Signaling Pathway in Experimental Rat Traumatic Optic Neuropathy

Wu

¹

,

Gu

²

,

Li

³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Activation of the nerve growth factor (NGF) signaling pathway is a potential method of treatment for retinal ganglion cell (RGC) loss due to traumatic optic neuropathy (TON). The present study aimed to explore the biological effects of injecting Astragalus membranaceus (A. mem) on RGCs in an experimental TON model. Adult male Wistar rats were randomly divided into three groups: sham-operated (SL), model (ML), and A. mem injection (AL). The left eyes of the rats were considered the experimental eyes, and the right eyes served as the controls. AL rats received daily intraperitoneal injections of A. mem (3 mL/kg), whereas ML and SL rats were administered the same volume of normal saline. The TON rat model was induced by optic nerve (ON) transverse quantitative traction. After two-week administration, the number of RGCs was determined using retrograde labeling with Fluoro-Gold. The protein levels of NGF, tyrosine kinase receptor A (TrkA), c-Jun N-terminal protein kinase (JNK), JNK phosphorylation (p-JNK), and nuclear factor kappa-B (NF-κB) were assessed using western blotting. The levels of p75 neurotrophin receptor (p75NTR) and NF-κB DNA binding were examined using real-time PCR and an electrophoretic mobility shift assay. In addition, the concentrations of JNK and p-JNK were assessed using an enzyme-linked immunosorbent assay. Results. The number of RGCs in ML was found to be significantly decreased P < 0.01 relative to both AL and SL, together with the downregulation of NGF P < 0.01 , TrkA P < 0.05 , and NF-κB P < 0.01 ; upregulation of p75NTR mRNA P < 0.01 ; and increased protein levels of JNK P < 0.05 and p-JNK P < 0.05 . Treatment using A. mem injection significantly preserved the density of RGCs in rats with experimental TON and markedly upregulated the proteins of NGF P < 0.01 , TrkA P < 0.05 , and NF-κB P < 0.01 and downregulated the mRNA level of p75NTR P < 0.01 , as well as the proteins of JNK P < 0.05 and p-JNK P < 0.01 . Thus, A. mem injection could reduce RGC death in TON induced by ON transverse quantitative traction by stimulating the NGF signaling pathway.

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Indirect traumatic optic neuropathy: modeling optic nerve injury in the context of closed head trauma

Cited by 14 publications

References 11 publications

Axonopathy precedes cell death in ocular damage mediated by blast exposure

Axonopathy precedes cell death in ocular damage mediated by blast exposure

Galantamine protects against synaptic, axonal, and vision deficits in experimental neurotrauma

Astragalus membranaceus Injection Protects Retinal Ganglion Cells by Regulating the Nerve Growth Factor Signaling Pathway in Experimental Rat Traumatic Optic Neuropathy

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