Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Transection is Driven by Cellular Intravitreal Sciatic Nerve Grafts
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Authors
Colleges, School and Institutes
Abstract
Neurotrophic factors (NTF) secreted by Schwann cells in a sciatic nerve (SN) graft promote
retinal ganglion cell (RGC) axon regeneration after either transplantation into the vitreous body of
the eye or anastomosis to the distal stump of a transected optic nerve. In this study, we investigated
the neuroprotective and growth stimulatory properties of SN grafts in which Schwann cells had
been killed (acellular SN grafts, ASN) or remained intact (cellular SN grafts, CSN). We report that
both intravitreal (ivit) implanted and optic nerve anastomosed CSN promote RGC survival and
when simultaneously placed in both sites, they exert additive RGC neuroprotection. CSN and ASN
were rich in myelin-associated glycoprotein (MAG) and axon growth-inhibitory ligand common to
both the central nervous system (CNS) and peripheral nervous system (PNS) myelin. The
penetration of the few RGC axons regenerating into an ASN at an optic nerve transection (ONT) site
is limited into the proximal perilesion area, but is increased >2-fold after ivit CSN implantation and
increased 5-fold into a CSN optic nerve graft after ivit CSN implantation, potentiated by growth
disinhibition through the regulated intramembranous proteolysis (RIP) of p75NTR (the signalling
trans-membrane moiety of the nogo-66 trimeric receptor that binds MAG and associated
suppression of RhoGTP). Mϋller cells/astrocytes become reactive after all treatments and maximally
after simultaneous ivit and optic nerve CSN/ASN grafting. We conclude that simultaneous ivit CSN
plus optic nerve CSN support promotes significant RGC survival and axon regeneration into CSN
optic nerve grafts, despite being rich in axon growth inhibitory molecules. RGC axon regeneration
is probably facilitated through RIP of p75NTR, which blinds axons to myelin-derived axon growthinhibitory
ligands present in optic nerve grafts.
Details
Original language | English |
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Article number | 1335 |
Journal | Cells |
Volume | 9 |
Issue number | 6 |
Publication status | Published - 27 May 2020 |
Keywords
- CNS, axon regeneration, neuroprotection, neurotrophic factors, optic nerve, optic nerve transection, peripheral nerve grafts, retinal ganglion cells