Erythropoietin is expressed in the human retina and it is highly elevated in the vitreous fluid of patients with diabetic macular edema.
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.
Hernández
Cristina
C
Diabetes Research Unit, Endocrinology Division, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Fonollosa
Alex
A
García-Ramírez
Marta
M
Higuera
Mónica
M
Catalán
Roberto
R
Miralles
Adela
A
García-Arumí
José
J
Simó
Rafael
R
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
D012333:RNA, Messenger; D004921:Erythropoietin