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J Neurosci Methods. 2019 Feb 1;313:1-5. doi: 10.1016/j.jneumeth.2018.10.038. Epub 2018 Oct 31.

Direct targeting of the mouse optic nerve for therapeutic delivery.

Author information

1
Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.
2
Department of Neurosurgery Stanford University School of Medicine, Palo Alto, CA, USA.
3
Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA.
4
Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA; Department of Neurology, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: yjliao@stanford.edu.

Abstract

BACKGROUND:

Animal models of optic nerve injury are often used to study central nervous system (CNS) degeneration and regeneration, and targeting the optic nerve is a powerful approach for axon-protective or remyelination therapy. However, the experimental delivery of drugs or cells to the optic nerve is rarely performed because injections into this structure are difficult in small animals, especially in mice.

NEW METHOD:

We investigated and developed methods to deliver drugs or cells to the mouse optic nerve through 3 different routes: a) intraorbital, b) through the optic foramen and c) transcranial.

RESULTS:

The methods targeted different parts of the mouse optic nerve: intraorbital proximal (intraorbital), intracranial middle (optic-foramen) or intracranial distal (transcranial) portion.

COMPARISON WITH EXISTING METHODS:

Most existing methods target the optic nerve indirectly. For instance, intravitreally delivered cells often cannot cross the inner limiting membrane to reach retinal neurons and optic nerve axons. Systemic delivery, eye drops and intraventricular injections do not always successfully target the optic nerve. Intraorbital and transcranial injections into the optic nerve or chiasm have been performed but these methods have not been well described. We approached the optic nerve with more selective and precise targeting than existing methods.

CONCLUSIONS:

We successfully targeted the murine optic nerve intraorbitally, through the optic foramen, and transcranially. Of all methods, the injection through the optic foramen is likely the most innovative and fastest. These methods offer additional approaches for therapeutic intervention to be used by those studying white matter damage and axonal regeneration in the CNS.

KEYWORDS:

Intraorbital; Optic foramen; Optic nerve injections; Transcranial injection

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