Erythropoietin is both neuroprotective and neuroregenerative following optic nerve transection.
The cytokine hormone erythropoietin (EPO) is neuroprotective in models of brain injury and disease, and protects retinal ganglion cells (RGC) from cell death after axotomy. Here, we assessed EPO's neuroprotective properties in vivo by examining RGC survival and axon regeneration at 4 weeks following intraorbital optic nerve transection in adult rat. EPO was administered as a single intravitreal injection at the time of transection (5, 10, 25, 50 units, PBS control). Intravitreal EPO (5, 10 units) significantly increased RGC somata and axon survival between the eye and transection site. Twenty five units did not improve survival of RGC somata but did increase axon survival between the eye and transection site. In addition, a small proportion of axons penetrated the transection site and regenerated up to 1 mm into the distal nerve. In a second series, intravitreal EPO (25 units) doubled the number of RGC axons regenerating along a length of peripheral nerve grafted onto the retrobulbar optic nerve. Our in vivo evidence of both neuroregeneration and neuroprotection, taken together with the natural occurrence of EPO within the body and its ability to cross the blood-brain barrier, suggests that it offers promise as a therapeutic agent for central nerve repair.
King
Carolyn E
CE
School of Animal Biology, University of Western Australia, Nedlands, Western Australia.
Rodger
Jennifer
J
Bartlett
Carole
C
Esmaili
Tammy
T
Dunlop
Sarah A
SA
Beazley
Lyn D
LD
D000818:Animals; D003714:Denervation; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D009416:Nerve Regeneration; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009900:Optic Nerve / Q000187:drug effects* / Q000503:physiopathology*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000503:physiopathology* / Q000601:surgery; D010543:Peroneal Nerve / Q000637:transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D012165:Retinal Ganglion Cells / Q000187:drug effects; D014822:Vitreous Body
D018696:Neuroprotective Agents; D004921:Erythropoietin