07-23-2002, 01:58 PM
• Junk AK, Mammis A, Savitz SI, Singh M, Roth S, Malhotra S, Rosenbaum PS, Cerami A, Brines M and Rosenbaum DM (2002). Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci U S A. Summary: Contributed by Anthony Cerami, May 29, 2002 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. *Departments of Neurology, Neuroscience, and Ophthalmology, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; paragraph signDepartments of Ophthalmology and Pathology, Albert Einstein College of Medicine, Bronx, NY 10461; and ||The Kenneth S. Warren Institute, 712 Kitchawan Road, Kitchawan, NY 10592.