Erythropoietin exerts endogenous neuroprotection after ocular hypertension induced glaucoma and optic nerve transection injuries

Abstract

Purpose: Erythropoietin (EPO) has been viewed traditionally as a hematopoietic cytokine in response to hypoxia. Results of recent studies have showed that EPO plays an important role to protect neurons after central nervous system (CNS) injuries. Here we report the role of EPO/EPO–receptor (EPO–R) system in the rat retina after chronic ocular hypertension and acute optic nerve transection injuries. Methods: Experimental glaucoma was induced by elevating the intraocular pressure (IOP). Two times of laser photocoagulation were provided to the episcleral and limbal veins with 7days interval. We tested the effect of recombinant human EPO (rhEPO) on survival of retinal ganglion cells (RGCs) after ocular hypertension (chronic injury) and optic nerve transection (acute injury). Results: Systemic administration of rhEPO before and immediately after retinal injuries significantly reduced the loss of RGCs in the glaucoma model at 2 weeks after injury and also promoted the survival of RGCs at 1 week after optic nerve transection. We identified Müller cells as the main cellular source of EPO in the normal retina. The levels of EPO–R in the retina significantly increased at 2 weeks after ocular hypertension, especially in RGCs. Moreover, neutralization of endogenous EPO with soluble EPO–R exacerbated ocular hypertensive injury, which provides evidence supportive of an endogenous EPO/EPO–R system in the survival and recovery of RGCs after injury. Conclusions: This results indicate that an endogenous EPO/EPO–R system participate in intrinsic recovery mechanisms after retina injury and RGCs might be rescued by exogenous administration of EPO.