Original article
Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders

https://doi.org/10.1016/S0002-9394(02)01323-5Get rights and content

Abstract

PURPOSE: To investigate the correlation between angiotensin II (AII) or vascular endothelial growth factor (VEGF) levels in the vitreous fluid and the severity of diabetic macular edema (DME).

DESIGN: A case-control study.

METHODS: Vitreous fluid samples were obtained at the time of vitreoretinal surgery from 20 eyes of 20 patients with DME, 6 eyes of 6 diabetic patients without retinopathy, and 14 eyes of 14 nondiabetic patients. The VEGF levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay, while AII levels were measured by radioimmunoassay.

RESULTS: The vitreous concentration of VEGF was significantly higher in patients with DME than in nondiabetic patients or diabetic patients without retinopathy (P < .0001 and P < .0001, respectively). Vitreous levels of AII were also higher in patients with DME than in nondiabetic patients (P = .0082). The vitreous concentration of AII was significantly correlated with that of VEGF (P = .0022). Vitreous concentrations of both AII and VEGF were significantly higher in patients with hyperfluorescent DME than in those with hypofluorescent (P = .0228 and P = .0068, respectively).

CONCLUSIONS: We found that the levels of both AII and VEGF were elevated in the vitreous fluid of patients with hyperfluorescein DME. Our results suggest that both AII and VEGF are related to the increase of vascular permeability in DME.

Section snippets

Subjects

Undiluted vitreous fluid samples were harvested at the start of vitrectomy after informed consent was obtained from each subject following an explanation of the purpose and potential adverse effects of the procedure. This study was performed in accordance with the Helsinki Declaration of 1975, as revised in 1983, and institutional review board approval was obtained. The vitreous fluid samples were obtained from 20 eyes of 20 patients with DME, 6 eyes of 6 diabetic patients without diabetic

Vitreous levels of VEGF and AII

The vitreous concentrations of VEGF were significantly elevated in the samples from patients with macular edema (861.0 pg/ml [38.8–1936.5]) when compared with the samples from nondiabetic patients (16.7 pg/ml [15.6–20.8] (P < .0001) or diabetic patients without retinopathy (47.9 pg/ml [23.4 to 95.6]) (P < .0001) (Figure 1, left). Vitreous concentrations of AII were also significantly elevated in the macular edema patients (22.8 pg/ml [8.0–79.0]) when compared with nondiabetic patients (9.5

Discussion

In diabetic patients, breakdown of the BRB and increased vascular permeability often lead to DME and visual loss. We hypothesized that AII may induce an increase of vascular permeability through a paracrine effect on VEGF in patients with DME. This study showed that vitreous VEGF levels were significantly elevated in patients with DME when compared with nondiabetic patients or diabetic patients without retinopathy. It has been already reported that vitreous VEGF levels are elevated in patients

Acknowledgements

We thank Drs. Erika Shimizu, Kensuke Haruyama, and Shinko Nakamura for their assistance in collecting the vitreous and plasma samples and in performing the ophthalmologic examinations. We also thank Drs. Yasuhiko Iwamoto and Naoko Iwasaki for their assistance in performing the internal medical examinations. Finally, we would like to thank Katsunori Shimada for his assistance in conducting the statistical analysis.

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    This study was supported by a Health Science Research Grant (#10060101 to H.F., S.H., H.Y.) from the Japanese Ministry of Health, Labor, and Welfare.

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