Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.
Department of Neurosurgery Stanford University School of Medicine, Palo Alto, CA, USA.
J Neurosci Methods. 2019 Feb 1;313:1-5. doi: 10.1016/j.jneumeth.2018.10.038. Epub 2018 Oct 31.
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.
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.
The methods targeted different parts of the mouse optic nerve: intraorbital proximal (intraorbital), intracranial middle (optic-foramen) or intracranial distal (transcranial) portion.
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.
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.
视神经损伤的动物模型常用于研究中枢神经系统（CNS）变性和再生，而靶向视神经是一种强大的轴突保护或髓鞘再生治疗方法。然而，由于向该结构注射药物或细胞的实验操作在小动物中很少进行，尤其是在小鼠中。
我们研究并开发了通过 3 种不同途径将药物或细胞递送至小鼠视神经的方法：a）眶内，b）经视神经孔和 c）颅穿。
这些方法靶向了小鼠视神经的不同部位：眶内近端（眶内）、颅内中部（视神经孔）或颅内远端（颅穿）。
大多数现有方法间接靶向视神经。例如，玻璃体内递送的细胞通常不能穿过内界膜到达视网膜神经元和视神经轴突。全身给药、滴眼和脑室注射并不总能成功靶向视神经。已经进行了眶内和颅穿视神经或视交叉注射，但这些方法尚未得到很好的描述。与现有方法相比，我们采用了更具选择性和精确性的方法来靶向视神经。
我们成功地通过眶内、经视神经孔和颅穿靶向了小鼠视神经。在所有方法中，经视神经孔注射可能是最具创新性和最快的方法。这些方法为研究中枢神经系统白质损伤和轴突再生的人员提供了额外的治疗干预途径。
