title: Erythropoietin is expressed in the human retina and it is highly elevated in the vitreous fluid of patients with diabetic macular edema.
abstract: 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 predominant event, and 2) to compare erythropoietin mRNA expression between human retinas from nondiabetic and diabetic donors without retinopathy.
  
  
  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.
authors.affiliation: Diabetes Research Unit, Endocrinology Division, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.forename: Alex
authors.initials: A
authors.lastname: Fonollosa
authors.forename: Marta
authors.initials: M
authors.lastname: García-Ramírez
authors.forename: Mónica
authors.initials: M
authors.lastname: Higuera
authors.forename: Roberto
authors.initials: R
authors.lastname: Catalán
authors.forename: Adela
authors.initials: A
authors.lastname: Miralles
authors.forename: José
authors.initials: J
authors.lastname: García-Arumí
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008269:Macular Edema / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D012333:RNA, Messenger; D004921:Erythropoietin