Abstract
Purpose :
Reforming retinofugal projections is essential to restoring vision. Unfortunately, spontaneous regeneration of the injured optic nerve in mammals does not occur. Stem cells have the potential to overcome this barrier by forming “optic nerve relays” that bridge the distance between injured retinal ganglion cell axons and terminal, centrally located, vision-associated nuclei. This study aims to assess the capacity of human neural stem cells (hNSCs) transplanted into the transected optic nerve to integrate with the host and extend axons into distal central nervous system targets.
Methods :
Human neural stem cells constitutively expressing a fluorescent protein, tdTomato, were acutely transplanted into the transected optic nerves of athymic nude rats. Graft survival within the optic nerve and extension of axons along the visual system were assessed six weeks post transplantation by immunohistochemistry and immunolabelling for tdTomato, neuronal and axonal markers (e.g., βIII-tubulin, human tau, etc.), and synaptic markers (e.g., postsynaptic density protein-95, vesicular glutamate transporter 1/2, etc.).
Results :
Human neural stem cells survive transplantation into the transected optic nerve for at least six weeks following grafting. The transplanted hNSCs differentiate into neurons and extend axons along the length of the optic nerve. By six weeks post transplantation, hNSC-derived axons extended into and beyond the optic chiasm. Retrochiasmal hNSC-derived axons were observed within the suprachiasmatic nucleus. Additionally, graft-derived axons were present in and followed the trajectory of the optic tract. At this early time point post transplantation, hNSC-derived axons were not observed in more distal targets such as the superior colliculus or lateral geniculate nucleus.
Conclusions :
Human neural stem cells survive engraftment into the lesioned optic nerve, have the capacity to differentiate into neurons, and extend projections that innervate retrochiasmal targets in the rodent. Optic nerve transplanted hNSCs have the potential to reinnervate vision-associated central nuclei and form bridges or relays between host retinal ganglion cells and retinofugal targets. Additional studies are needed to assess graft long-term survival, electrophysiological function, and impact on behavioral outcomes.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.