Hypoxic induction of vascular endothelial growth factor is markedly decreased in diabetic individuals who do not develop retinopathy.
OBJECTIVE
A small percentage of patients do not develop any evidence of diabetic retinopathy (DR) even after many years of diabetes. Vascular endothelial growth factor (VEGF) has been implicated in the development of DR. Therefore, we sought to determine if the regulation of VEGF differs in those patients who develop DR after many years of diabetes compared with those who do not develop DR.


METHODS
We performed standard 7-field stereoscopic fundus photography on 95 consecutive patients with type 1 and type 2 diabetes. Patients were categorized into 3 groups according to the presence or absence of DR and the duration of diabetes: group 1 was defined by presence of DR, group 2 was defined by absence of DR after >10 years duration of diabetes, and group 3 was defined by absence of DR with long-standing diabetes (> or =20 years for type 1 diabetes and > or =15 years for type 2 diabetes). Monocytes from 40 ml peripheral blood were isolated from all patients, and the hypoxic induction of VEGF was determined in vitro.


RESULTS
We found no significant difference in the basal level of VEGF in patients with and without DR. However, we did find a markedly significant difference in the hypoxic induction of VEGF between patients from group 1 and group 3 (4.35+/-0.55 vs. 1.87+/-0.3, P<0.00013).


CONCLUSIONS
This study suggests that 1 mechanism for the absence of DR in patients with long-standing diabetes is a decreased hypoxic induction of VEGF.
Marsh
S
S
Department of Nephrology and Molecular Medicine, Rambam Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
Nakhoul
F M
FM
Skorecki
K
K
Rubin
A
A
Miller
B P
BP
Leibu
R
R
Levy
N S
NS
Levy
A P
AP
D015687:Cell Hypoxia / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D066298:In Vitro Techniques; D008222:Lymphokines / Q000096:biosynthesis / Q000097:blood*; D008297:Male; D009000:Monocytes / Q000502:physiology*; D010781:Photography; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors