Abstract
Purpose :
Neural development has a strict relationship between initial axon growth resulting in postsynaptic innervation, and subsequent dendritic development. In contrast, axons of the adult mammalian central nervous system fail to regenerate after injury, perhaps as a result of the inability to replicate the developmental timeline after injury. However, the relationship between developmental growth and neural response to injury remains elusive. In addition, in the mouse retina, of the ~40 molecularly identified retinal ganglion cell (RGC) types, the 4 alpha-RGCs survive best, but each has a different resilience to injury. Here, we use mouse alpha-RGCs and the optic nerve crush as a model to investigate the relationship between development and the response to injury in transcriptionally similar cells.
Methods :
In this study, we have characterized the dendritic morphology of mouse RGCs during development and in response to injury, reconstructing thousands of RGC dendrites at different stages of development and times after injury. Several parameters were chosen to describe each cell's characteristics, including total dendritic length, number of branching points, number of branches, dendritic field, and soma size. A minimum spanning tree model was used to characterize the dendritic morphology at different stages of development. We found that for each cell type the dendritic architecture remains consistent throughout development, with cells increasing in size uniformly in all directions.
Results :
We found that, during development, all RGC dendrites reach mature length at eye-opening, but the timing of their dendritic growth onset and speed varies. Subsequently, we found that all RGCs shrink in response to injury (optic nerve crush), but each cell type shrinks at a different rate. Using the same minimum spanning tree model used to characterize dendritic structure during development, we saw that key relationships of their dendritic structure break down during the initial response to injury. By comparing the minimum spanning tree model created during development with the dendritic profile changes after injury we saw that the cells that regenerate the most, more closely replicate the rules of development.
Conclusions :
Taken together, the differences in response to injury and growth timings during development may explain the variance in the resilience of each ganglion cell type.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.