TNF inhibition improves neuron survival in mice with optic nerve trauma

This mouse study explored whether etanercept, a tumor necrosis factor (TNF) inhibitor, can protect retinal ganglion cells (RGCs) and improve visual outcomes after optic nerve trauma.

Study design

Mouse optic nerves were unilaterally subjected to optic nerve crush (ONC) or sonication-induced traumatic optic neuropathy (SI-TON). In half of the mice, TNF expression was measured using immunohistochemistry and quantitative RT-PCR in optic nerves that were harvested 6 and 24 hours after ONC or SI-TON. In the other half of the mice, 1 group received subcutaneous injection of etanercept or vehicle (control). Pattern electroretinograms were performed on all mice after injury. Whole retina flat-mounts were performed for RGC quantification after the mice were euthanized.  

Outcomes

Upregulation of TNF protein and gene expression were noted by immunohistochemistry and qRT-PCR, respectively, within 24 hours after injury. Etanercept use increased RGC numbers relative to controls for both types of injury. In addition, both groups had significantly higher a-wave amplitudes than untreated injured controls.

Limitations

This study suggests that entercept improves the survival of RGCs in mice with ONC and SI-TON injuries. It is unclear whether this model of optic nerve injury is analogous to the traumatic optic neuropathy seen in humans. A prospective, randomized, case-controlled human study is needed. 

Clinical significance

At this point in time, there is no effective treatment for traumatic optic neuropathy (i.e., indirect optic nerve injury) in humans. Although surgical decompression of the optic nerve canal and treatment with high-dose corticosteroids have been proposed as possible treatments, neither have been shown to be effective. This study offers promise that the use of a TNF-inhibitor may help treat traumatic optic neuropathy in humans.