Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic.
Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (IVZ), protects RGC from apoptosis and stimulates axon regeneration after optic nerve transection. Here, we investigate the differential effects of intra-optic nerve zymosan (ONZ) and IVZ injections on RGC neuroprotection and axogenesis. After both IVZ and ONZ injection, zymosan-induced inflammation promoted a similar 4-/5-fold enhancement in RGC survival, compared to optic nerve transected controls, but only IVZ promoted RGC axon regeneration. IVZ was the most effective in activating retinal astrocyte/Müller cells while regulated intramembraneous proteolysis (RIP) of p75(NTR) and inactivation of Rho (key components of the axon growth inhibitory signalling cascade) occurred in both ONZ and IVZ, but only in the latter did RGC axons regenerate. We suggest that neuroprotective factors may be transported to RGC somata by retrograde transport after ONZ and diffuse into the retina after IVZ injection, but an axogenic agent is required to initiate and maintain disinhibited RGC axon regeneration that may be an exclusive property of a Müller cell-derived factor released after IVZ.
Ahmed
Zubair
Z
Molecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. z.ahmed.1@bham.ac.uk
Aslam
Mudasser
M
Lorber
Barbara
B
Suggate
Ellen L
EL
Berry
Martin
M
Logan
Ann
A
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001370:Axonal Transport / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000633:toxicity; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009902:Optic Neuritis / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014822:Vitreous Body / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D015054:Zymosan / Q000633:toxicity; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D015054:Zymosan; D020741:rho GTP-Binding Proteins