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Erythropoietin Is Expressed in the Human Retina and It Is Highly Elevated in the Vitreous Fluid of Patients With Diabetic Macular Edema

¹ Diabetes Research Unit, Endocrinology Division, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
² Ophthalmology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
³ Biochemistry Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
⁴ Tissue Bank and Cell Therapy Center, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

Address correspondence and reprint requests to Dr. Rafael Simó, Diabetes Research Unit, Endocrinology Division, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, 08035 Barcelona, Spain. E-mail: rsimo{at}ir.vhebron.net

OBJECTIVE—Erythropoietin has been recently found to be increased in the vitreous fluid from ischemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aims of the present study were 1) to measure erythropoietin levels in the vitreous fluid from patients with diabetic macular edema (DME), a condition in which the ischemia is not a predominat event, and 2) to compare erythropoietin mRNA expression between human retinas from nondiabetic and diabetic donors without retinopathy.

RESEARCH DESIGN AND METHODS—Vitreous samples from 12 type 2 diabetic patients with DME without significant retinal ischemia and 12 PDR patients were prospectively analyzed. Ten nondiabetic patients with macular holes served as the control group. Erythropoietin was assessed by radioimmunoassay (milliunits per milliliter). Erythropoietin mRNA expression was measured by quantitative real-time RT-PCR analysis in the retina from eight nondiabetic and eight age-matched diabetic donors without diabetic retinopathy

RESULTS—Intravitreal erythropoietin concentration was higher in both PDR and DME patients than in nondiabetic control subjects (PDR vs. control subjects: median 302 [range 117–1,850] vs. 30 mU/ml [10–75], P < 0.01; DME vs. control subjects: 430 [41–3,000] vs. 30 mU/ml [10–75], P < 0.01). However, no significant differences were found between DME and PDR patients. Erythropoietin mRNA expression was detected in the human retina, and it was higher in the retina from diabetic than from nondiabetic donors.

CONCLUSIONS—As occurs in PDR, intravitreous erythropoietin concentrations are strikingly higher in DME. Erythropoietin is expressed in the human retina, and it is upregulated in diabetic patients even without retinopathy. These findings suggest that other factors apart from ischemia are involved in the overexpression of erythropoietin in diabetic retinopathy.

Abbreviations: BBB, blood-brain barrier • BRB, blood-retinal barrier • DME, diabetic macular edema • PDR, proliferative diabetic retinopathy • RPE, retinal pigment epithelium • VEGF, vascular endothelial growth factor

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