Laboratories for Neuroscience Research in Neurosurgery and F.M. Kirby Neurobiology Center, Children's Hospital, Boston, Massachusetts, USA.
Int Rev Neurobiol. 2012;106:153-72. doi: 10.1016/B978-0-12-407178-0.00007-7.
The optic nerve has been widely studied for insights into mechanisms that suppress or promote axon regeneration after central nervous system injury. Following optic nerve damage in adult mammals, retinal ganglion cells (RGCs) normally fail to regenerate their axons, resulting in blindness in patients who suffer from neurodegenerative diseases such as glaucoma or who have sustained traumatic injury to the optic nerve. Over the past several decades, many groups have investigated the basis of regenerative failure in the hope of developing strategies to stimulate the regrowth of axons and restore visual function. New findings show that a combination of therapies that act synergistically to activate RGCs' intrinsic growth state enables these cells to regenerate their axons the full length of the optic nerve, across the optic chiasm, and into the brain, where they establish synapses in appropriate target zones and restore limited visual responses. These treatments involve the induction of a limited inflammatory response in the eye to increase levels of oncomodulin and other growth factors; elevation of intracellular cAMP; and deletion of the pten gene in RGCs. Although these methods cannot be applied in the clinic, they point to strategies that might be.
视神经已被广泛研究，以深入了解中枢神经系统损伤后抑制或促进轴突再生的机制。在成年哺乳动物的视神经损伤后，视网膜神经节细胞（RGCs）通常无法再生其轴突，导致患有青光眼等神经退行性疾病或视神经受到创伤的患者失明。在过去的几十年中，许多研究小组研究了再生失败的基础，希望开发出刺激轴突再生和恢复视觉功能的策略。新发现表明，多种协同作用的疗法可激活 RGCs 的内在生长状态，使这些细胞能够再生其全长视神经、穿过视交叉并进入大脑，在那里它们在适当的靶区建立突触并恢复有限的视觉反应。这些治疗方法涉及在眼睛中诱导有限的炎症反应以增加脑源性神经营养因子和其他生长因子的水平；提高细胞内 cAMP 水平；以及在 RGC 中删除 pten 基因。虽然这些方法不能在临床上应用，但它们为可能的策略指明了方向。
