Up-regulated endogenous erythropoietin/erythropoietin receptor system and exogenous erythropoietin rescue retinal ganglion cells after chronic ocular hypertension.
OBJECTIVE
Recent studies have showed that erythropoietin (EPO) is a neuroprotectant for central nerve system neurons in addition to being a hematopoietic cytokine in response to hypoxia. In this study, we investigate the role of the EPO/EPO receptor (EPOR) system in the rat retina after ocular hypertension injury that mimics glaucoma.


METHODS
Elevated intraocular pressure was induced by laser coagulation of the episcleral and limbal veins. Expression of EPO and EPOR in the normal and glaucomous retinas was investigated by immunohistochemistry and Western blot. To examine the effects of endogenous EPO on the survival of retinal ganglion cells (RGCs) subjected to hypertensive injury, soluble EPOR was directly injected into the vitreous body. Recombinant human EPO was both intravitreally and systemically administrated to study the effect of exogenous EPO on the survival of RGCs after ocular hypertension injury.


RESULTS
Immunohistochemistry studies identified Müller cells as the main source of EPO in the normal retina. Expression of EPO and EPOR proteins was increased significantly 2 weeks after ocular hypertension. RGCs, amacrine and bipolar cells all demonstrated an increased expression of EPOR after ocular hypertension. Neutralization of endogenous EPO with soluble EPOR exacerbated ocular hypertensive injury, suggesting a role of the EPO/EPOR system in the survival of RGCs after injury. Similarly, topical and systemic administration of recombinant human EPO rescues RGCs after chronic ocular hypertension.


CONCLUSIONS
These results indicate that an endogenous EPO/EPOR system participates in intrinsic recovery mechanisms after retina injury and RGCs might be rescued by exogenous administration of EPO.
Fu
Qing-Ling
QL
Department of Anatomy, The University of Hong Kong Li Ka Shing Faculty of Medicine, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
Wu
Wutian
W
Wang
Hua
H
Li
Xin
X
Lee
Vincent W H
VW
So
Kwok-Fai
KF
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D004921:Erythropoietin / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D018696:Neuroprotective Agents / Q000494:pharmacology; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020221:Optic Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D012995:Solubility; D015854:Up-Regulation / Q000502:physiology
D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D004921:Erythropoietin