Traumatic Optic Neuropathy

Jang, Sun Young

doi:10.13004/kjnt.2018.14.1.1

Cited by 22 publications

(18 citation statements)

References 32 publications

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“…The irreversible effects of traumatic optic neuropathy (TON) can result from direct impulse or indirectly by shearing or stretch of the optic nerve [ 1 ]. Although this type of injury can occur in any age group, most TON occurs in young males under the age of 18, resulting in a range of visual outcomes from unaffected to substantial vision loss.…”

Section: Introductionmentioning

confidence: 99%

Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1

et al. 2021

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SIRT1 prevents retinal ganglion cell (RGC) loss in models of optic neuropathy following pharmacologic activation or genetic overexpression. The exact mechanism of loss is not known, prior evidence suggests this is through oxidative stress to either neighboring cells or RGC specifically. We investigated the neuroprotective potential of RGC-selective SIRT1 gene therapy in the optic nerve crush (ONC) model. We hypothesized that AAV-mediated overexpression of SIRT1 in RGCs reduces RGC loss, thereby preserving visual function. Cohorts of C57Bl/6J mice received intravitreal injection of experimental or control AAVs using either a ganglion cell promoter or a constitutive promoter and ONC was performed. Visual function was examined by optokinetic response (OKR) for 7 days following ONC. Retina and optic nerves were harvested to investigate RGC survival by immunolabeling. The AAV7m8-SNCG.SIRT1 vector showed 44% transduction efficiency for RGCs compared with 25% (P > 0.05) by AAV2-CAG.SIRT1, and AAV7m8-SNCG.SIRT1 drives expression selectively in RGCs in vivo. Animals modeling ONC demonstrated reduced visual acuity compared to controls. Intravitreal delivery of AAV7m8-SNCG.SIRT1 mediated significant preservation of the OKR and RGC survival compared to AAV7m8-SNCG.eGFP controls, an effect not seen with the AAV2 vector. RGC-selective expression of SIRT1 offers a targeted therapy for an animal model with significant ganglion cell loss. Over-expression of SIRT1 through AAV-mediated gene transduction suggests a RGC selective component of neuro-protection using the ONC model. This study expands our understanding of SIRT1 mediated neuroprotection in the context of compressive or traumatic optic neuropathy, making it a strong therapeutic candidate for testing in all optic neuropathies.

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Section: Introductionmentioning

confidence: 99%

Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1

et al. 2021

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“…However, there is no damage to the ocular and cerebral tissue [ 33 , 39 ]. Indirect TON can occur when there is concussive trauma to the forehead [ 40 , 41 ] or a blast-TBI. The neuropathology of an indirect TON can be distinguished from a direct TON [ 42 ].…”

Section: Tbi To Vision Loss: Pathophysiological Pathways and Biomechanical Mechanismsmentioning

confidence: 99%

“…There were also indirect injuries, although fewer than the number of direct injuries (9%). In general however, indirect TON is more commonly occurring than direct TON [ 41 ].…”

Section: Tbi To Vision Loss: Pathophysiological Pathways and Biomechanical Mechanismsmentioning

confidence: 99%

“…Diagnosing a TON is challenging. It is easier to diagnose a direct TON as there is usually - but not always - an open wound, and imaging methods such as computed tomography and magnetic resonance imaging can be used [ 41 ]. Imaging techniques such as optical coherence tomography (OCT) will show thinning of the retinal ganglion cell layer within weeks and retinal nerve fibre layer (RNFL) within months due to retrograde degeneration.…”

Section: Tbi To Vision Loss: Pathophysiological Pathways and Biomechanical Mechanismsmentioning

confidence: 99%

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Traumatic brain injury and sight loss in military and veteran populations– a review

Hussain¹,

Raza²,

Cash³

et al. 2021

Military Med Res

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War and combat exposure pose great risks to the vision system. More recently, vision related deficiencies and impairments have become common with the increased use of powerful explosive devices and the subsequent rise in incidence of traumatic brain injury (TBI). Studies have looked at the effects of injury severity, aetiology of injury and the stage at which visual problems become apparent. There was little discrepancy found between the frequencies or types of visual dysfunctions across blast and non-blast related groups, however complete sight loss appeared to occur only in those who had a blast-related injury. Generally, the more severe the injury, the greater the likelihood of specific visual disturbances occurring, and a study found total sight loss to only occur in cases with greater severity. Diagnosis of mild TBI (mTBI) is challenging. Being able to identify a potential TBI via visual symptoms may offer a new avenue for diagnosis.

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“…The current treatment for TON includes Ophthalmic Res 2021;64:398-404 DOI: 10.1159/000512469 conservative management, high-dose steroids, optic canal decompression, and combined management. Although medical and surgical treatments have certain effect in some cases, there is still no proven treatment for TON [4]. Optic canal decompression can relieve local obstruction and compression; however, it still cannot change glial scar formation caused by the injured local microenvironment as well as the apoptosis of retinal ganglion cells (RGCs) [5].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Optic Canal Decompression Combined with Umbilical Cord Mesenchymal Stem (Stromal) Cells for Indirect Traumatic Optic Neuropathy: A Phase 1 Clinical Trial

Li¹,

Bai²,

Guan³

et al. 2020

Ophthalmic Res

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Purpose: This study was aimed to investigate the safety and feasibility of umbilical cord-derived mesenchymal stem cell (MSC) transplantation in patients with traumatic optic neuropathy (TON). Methods: This is a single-center, prospective, open-labeled phase 1 study that enrolled 20 patients with TON. Patients consecutively underwent either optic canal decompression combined with MSC local implantation treatment (group 1) or only optic canal decompression (group 2). Patients were evaluated on the first day, seventh day, first month, third month, and sixth month postoperatively. Adverse events, such as fever, urticarial lesions, nasal infection, and death, were recorded at each visit. The primary outcome was changes in best-corrected visual acuity. The secondary outcomes were changes in color vision, relative afferent pupillary defect, and flash visual evoked potential. Results: All 20 patients completed the 6-month follow-up. None of them had any systemic or ocular complications. The change in best-corrected visual acuity at follow-up was not significantly different between group 1 and group 2 (p > 0.05); however, group 1 showed better visual outcome than group 2. Both groups showed significant improvements in vision compared with the baseline (p < 0.05); however, there were no statistically significant differences between the groups (p > 0.05). In addition, no adverse events related to local transplantation were observed in the patients. Conclusions: A single, local MSC transplantation in the optic nerve is safe for patients with TON.

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Traumatic Optic Neuropathy

Cited by 22 publications

References 32 publications

Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1

Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1

Traumatic brain injury and sight loss in military and veteran populations– a review

Treatment of Optic Canal Decompression Combined with Umbilical Cord Mesenchymal Stem (Stromal) Cells for Indirect Traumatic Optic Neuropathy: A Phase 1 Clinical Trial

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