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 EPO͞EPO-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. E rythropoietin (EPO) has been viewed traditionally as a hematopoietic cytokine produced by the fetal liver and adult kidney in response to hypoxia. Results of recent studies now support a physiological role for EPO within the central nervous system. The expression of EPO and EPO receptors (EPO-Rs) in the central nervous system and the up-regulation of EPO by hypoxia͞ischemia in vitro and in vivo suggest that this cytokine is an important mediator of the brain's response to injury. Consistent with this hypothesis, pretreatment with exogenous EPO protects cultured neurons from hypoxia (1, 2), glutamate excitotoxicity (3), and growth-factor withdrawal (2). When administered systemically, EPO can cross the blood-brain barrier and reduce neuronal injury in animal models of focal ischemic stroke, traumatic brain injury, inflammation, kainate toxicity, and spinal cord injury (2, 4, 5). EPO rescues neurons from acute injury at least in part by inhibiting apoptosis via activation of specific protein kinase pathways (2) and the recruitment of NF-B (6).Prior studies of EPO in different models of brain injury raise the possibility that this cytokine may participate in the recovery of retinal neurons from ischemia. Retinal ischemia is a serious and common clinical problem. It occurs as a result of acute vascular occlusion and leads to visual loss in a number of ocular diseases such as acute glaucoma (7), diabetic retinopathy (8), and hypertensive vascular disease (9). Transient global retinal ischemia, for example, shares many similarities with transient global cerebral ischemia. Both cause selective damage of specific subpopulations of neurons. Pyramidal neurons in the CA-1 zone of the hippocampus are selectively vulnerable to trans...

The eyes of a prospective cohort of 8,607 Chernobyl clean-up workers (liquidators) were assessed for cataract at 12 and 14 years after exposure. The prevalence of strictly age-related cataracts was low, as expected (only 3.9% had nuclear cataracts at either examination), since 90% of the cohort was younger than 55 years of age at first examination. However, posterior subcapsular or cortical cataracts characteristic of radiation exposure were present in 25% of the subjects. The data for Stage 1 cataracts, and specifically for posterior subcapsular cataracts, revealed a significant dose response. When various cataract end points were analyzed for dose thresholds, the confidence intervals all excluded values greater than 700 mGy. Linear-quadratic dose-response models yielded mostly linear associations, with weak evidence of upward curvature. The findings do not support the ICRP 60 risk guideline assumption of a 5-Gy threshold for "detectable opacities" from protracted exposures but rather point to a dose-effect threshold of under 1 Gy. Thus, given that cataract is the dose-limiting ocular pathology in current eye risk guidelines, revision of the allowable exposure of the human visual system to ionizing radiation should be considered.

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