Using stem cells to model the development and regeneration of retinal neurons
Photoreceptor (PR) transplantation is a promising treatment option for blindness caused by photoreceptor degeneration, including the most common cause of blindness in developed countries, Age-Related Macular Degeneration. While PR transplant research is ongoing and shows some promise, the success of this approach is hindered by a lack of knowledge about the basic mechanisms by which PR axons develop, extend, and are guided to their targets. By understanding the mechanisms that control PR neurite extension, we can better inform transplant therapies to ensure effective PR integration for functional sight restoration. Using stem cells we are generating retina-like optic vesicles, which contain all cell types within the retina, including late-born PRs. Currently we are using traditional methods to assess basic mechanisms of PR axon extension, combined with RNAseq data sets to identify molecular changes that may be responsible for age-dependent changes in PR axon outgrowth.
Current Open Questions:
- Do human Photoreceptors (PRs) generate axons by traditional cell autonomous terminal extension driven by motile growth cones?
- How does PR terminal growth change with developmental time and what molecular changes are responsible for loss of terminal motility?
- Does PR axon formation occur by similar developmental time-dependent changes within 3D retinal organoids?
- Can we influence young and old PR terminal extension behaviors through targeted molecular manipulations to promote PR regeneration?