Neurons that regenerate, neurons that die

“Our long term goal is to repair brain, spinal cord or eye injury by regenerating functional connections,” said Bei. “The goal will be to regenerate as many subtypes of neurons as possible. Our results here suggest that different subtypes of neurons may respond differently to the same factors. This may mean that when we reach the point of developing new therapies, we may need to consider combination therapies for optimal recovery.”

Previous studies using the optic nerve as a model for injury have found that manipulating transcription factors — the master control switches of genes — might represent a promising avenue for stimulating axon regeneration. In the current study, researchers focused on transcription factors likely to influence the early development of retinal ganglion cells (RGCs). There are at least 30 types of RGCs in the human eye, which control different aspects of vision, and the researchers were interested in the effects of transcription factors on various types of RGCs. Using a mouse model of optic nerve injury, the research team found that increasing the production of a transcription factor known as Sox11 appeared to help axons grow past the site of injury. However, the team observed that the very same transcription factor also efficiently killed a type of RGCs known as alpha-RGCs which would preferentially survive the injury if untreated.

Bei notes that the heterogeneity of the nervous system — the inclusion of different cells with different properties and functions — will be an important consideration as researchers work to reprogram and, ultimately, restore the optic nerve, brain or spinal cord after injury.