Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury.
Erythropoietin (EPO) plays an important role in the brain's response to neuronal injury. Systemic administration of recombinant human EPO (rhEPO) protects neurons from injury after middle cerebral artery occlusion, traumatic brain injury, neuroinflammation, and excitotoxicity. Protection is in part mediated by antiapoptotic mechanisms. We conducted parallel studies of rhEPO in a model of transient global retinal ischemia induced by raising intraocular pressure, which is a clinically relevant model for retinal diseases. We observed abundant expression of EPO receptor (EPO-R) throughout the ischemic retina. Neutralization of endogenous EPO with soluble EPO-R exacerbated ischemic injury, which supports a crucial role for an endogenous EPO/EPO-R system in the survival and recovery of neurons after an ischemic insult. Systemic administration of rhEPO before or immediately after retinal ischemia not only reduced histopathological damage but also promoted functional recovery as assessed by electroretinography. Exogenous EPO also significantly diminished terminal deoxynucleotidyltransferase-mediated dUTP end labeling labeling of neurons in the ischemic retina, implying an antiapoptotic mechanism of action. These results further establish EPO as a neuroprotective agent in acute neuronal ischemic injury.
Junk
Anna K
AK
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Mammis
Antonios
A
Savitz
Sean I
SI
Singh
Manjeet
M
Roth
Steven
S
Malhotra
Samit
S
Rosenbaum
Pearl S
PS
Cerami
Anthony
A
Brines
Michael
M
Rosenbaum
Daniel M
DM
D000818:Animals; D004921:Erythropoietin / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology*; D005123:Eye / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000517:prevention & control*; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D012995:Solubility
D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D004921:Erythropoietin