Traumatic Optic Neuropathy: An Evolving Understanding

Steinsapir, Kenneth D.; Goldberg, Robert A.

doi:10.1016/j.ajo.2011.02.007

Cited by 153 publications

(155 citation statements)

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“…1 Although spontaneous visual improvement occurs in a minority of patients, permanent visual impairment is frequent and currently there are no clinically effective treatments. [2][3][4] The RGC death, which commences within 5 to 6 days after ON injury with more than 90% RGC loss by 14 days, 5 is preventable by either downregulation of proapoptotic caspases [6][7][8] or upregulation of antiapoptotic mediators, such as Bcl-2 9,10 and Bcl-XL.…”

mentioning

confidence: 99%

siRNA-Mediated Knockdown of the mTOR Inhibitor RTP801 Promotes Retinal Ganglion Cell Survival and Axon Elongation by Direct and Indirect Mechanisms

Morgan-Warren

O'Neill

Cogan

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate, using in vivo and in vitro models, retinal ganglion cell (RGC) neuroprotective and axon regenerative effects and underlying mechanisms of siRTP801, a translatable small-interfering RNA (siRNA) targeting the mTOR negative regulator RTP801.METHODS. Adult rats underwent optic nerve (ON) crush (ONC) followed by intravitreal siRTP801 or control siRNA (siEGFP) every 8 days, with Brn3a þ RGC survival, GFAP þ reactive gliosis, and GAP43 þ regenerating axons analyzed immunohistochemically 24 days after injury. Retinal cultures, prepared from uninjured animals or 5 days after ONC to activate retinal glia, were treated with siRTP801/controls in the presence/absence of rapamycin and subsequently assessed for RGC survival and neurite outgrowth, RTP801 expression, glial responses, and mTOR activity. Conditioned medium was analyzed for neurotrophin titers by ELISA. RESULTS. Intravitreal siRTP801 enabled 82% RGC survival compared to 45% with siEGFP 24 days after ONC, correlated with greater GAP43þ axon regeneration at 400 to 1200 lm beyond the ONC site, and potentiated the reactive GFAP þ Müller glial response. In culture, siRTP801 had a direct RGC neuroprotective effect, but required GFAP þ activated glia to stimulate neurite elongation. The siRTP801-induced neuroprotection was significantly reduced, but not abolished, by rapamycin. The siRTP801 potentiated the production and release of neurotrophins NGF, NT-3, and BDNF, and prevented downregulation of RGC mTOR activity.CONCLUSIONS. The RTP801 knockdown promoted RGC survival and axon elongation after ONC, without increasing de novo regenerative sprouting. The neuroprotection was predominantly direct, with mTORC1-dependent and -independent components. Enhanced neurite/axon elongation by siRTP801 required the presence of activated retinal glia and was mediated by potentiated secretion of neurotrophic factors.

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confidence: 99%

siRNA-Mediated Knockdown of the mTOR Inhibitor RTP801 Promotes Retinal Ganglion Cell Survival and Axon Elongation by Direct and Indirect Mechanisms

Morgan-Warren

O'Neill

Cogan

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Despite of ocular manifestations, we have to perform CT scans examination as diagnostic procedure of choice TON to show if there is a bone fracture [15,17]. The three commonly recommended approaches for indirect TON are corticosteroid mega-doses, decompression of the optic canal and observation [15][16][17][18][19][20]. However, one should consider that patient should be informed of this unproven benefit and if there's no response, optic canal decompression through trans-ethmoidal route might be considered.…”

Section: Discussionmentioning

confidence: 99%

Inadequate Management of Multiple Orbital Fractures and Traumatic Optic Neuropathy

Irawati¹,

Tjintya²,

Suharko³

et al. 2017

JCR

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Background: The purpose of this case report is to demonstrate a re-surgery in patient with inadequate management of multiple orbital fractures and traumatic optic neuropathy as a way to relieve his visual problem. Case Report: A 25 year old male presented with double vision following surgical repair of orbital rim fracture. Right eye examination revealed restricted eye movement in all directions and visual acuity was 2/60. Improvement was noted in diplopia and visual acuity following surgery in our hospital to release tissue entrapment with silicone block implant. Conclusion: Management of multiple orbital fractures should be done simultaneously with multidisciplinary teams for adequate and appropriate management.

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“…In a large retrospective study of individuals with head injuries, about 2.3% of patients had TON and of these cases about 10% were bilateral (Pirouzmand 2012;Steinsapir and Goldberg 2011). The presence of a nasoethmoid fracture was positively associated as a risk factor for TON.…”

Section: Traumatic Optic Neuropathiesmentioning

confidence: 99%