SCIENTIFIC REPORT

Expression of erythropoietin receptor in human epiretinal membrane of proliferative diabetic retinopathy

Satoru Kase¹, Wataru Saito¹, Kazuhiro Ohgami¹, Kazuhiko Yoshida¹, Naoki Furudate¹, Akari Saito¹, Masahiko Yokoi², Manabu Kase² and Shigeaki Ohno¹

¹ Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638, Japan
² Department of Ophthalmology, Teine Keijin-kai Hospital, Sapporo, Japan

Correspondence to:
Satoru Kase, Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638 Japan; kaseron{at}med.hokudai.ac.jp

Purpose: It is widely accepted that intravitreous levels of erythropoietin (Epo) are elevated in patients with ischaemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aim of this study was to examine the expression of Epo and the Epo receptor (EpoR) in epiretinal membranes with and without diabetes.

Methods: Eighteen epiretinal membranes (PDR (n = 10), idiopathic epiretinal membranes (IERMs) without diabetes (n = 4) and inner limiting membranes (ILMs) (n = 4)) were obtained during pars plana vitrectomy. Formalin-fixed and paraffin-embedded tissues were examined by immunohistochemistry with anti-Epo and EpoR antibodies.

Results: The histopathological findings demonstrated that PDR membranes consisted of a variety of endothelial cells forming a microvascular cavity with red blood cells and non-vascular stromal mononuclear cells. Membranous and cytoplasmic immunoreactivity for EpoR was strongly detected in endothelial cells and stromal cells in all PDR patients. Although microvessels were not observed in IERMs and ILMs, immunoreactivity for EpoR was noted in the cellular component of IERMs, and was weakly detected in ILMs. Epo was not expressed in any membrane.

Conclusion: EpoR was strongly expressed in microvessels of all PDR membranes. The in vivo evidence in this study suggests that Epo in the vitreous binds to EpoR in PDR membranes, which subsequently leads to the proliferation of new retinal vessels. EpoR immunoreactivity in non-vascular stromal cells in PDR membranes, and IERMs and ILMs might be indirectly correlated with ischaemia.

Abbreviations: BREC, bovine retinal microvascular endothelial cells; Epo, erythropoietin; EpoR, erythropoietin receptor; IERM, idiopathic epiretinal membranes; ILM, inner limiting membranes; PDR, proliferative diabetic retinopathy

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