Elsevier

Ophthalmology

Volume 110, Issue 9, September 2003, Pages 1690-1696
Ophthalmology

Original article
Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema

https://doi.org/10.1016/S0161-6420(03)00568-2Get rights and content

Abstract

Purpose

To investigate whether interleukin-6 (IL-6) or vascular endothelial growth factor (VEGF) is related to diabetic macular edema (DME) in subjects without posterior vitreous detachment (PVD).

Design

Retrospective case-control study.

Participants

Twenty-six subjects who had DME without PVD and 12 subjects who had nondiabetic ocular disease (the control group).

Methods

Vitreous fluid samples were obtained at vitreoretinal surgery, and the IL-6 and VEGF levels in vitreous fluid and plasma were measured by enzyme-linked immunosorbent assay.

Main outcome measures

Vitreous levels of IL-6 and VEGF in DME subjects without PVD.

Results

The vitreous levels of both IL-6 and VEGF were significantly higher in the subjects with DME than in control subjects (P<0.0001 and P<0.0001, respectively). The vitreous level of IL-6 was significantly correlated with that of VEGF (P<0.0001). Vitreous levels of both IL-6 and VEGF were significantly higher in subjects with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0008 and P = 0.0038, respectively).

Conclusions

We found that the levels of both IL-6 and VEGF were elevated in the vitreous fluid of subjects with hyperfluorescent DME. Our results suggest that IL-6 and VEGF may promote an increase of vascular permeability in DME subjects without PVD. Interleukin-6 may possibly induce an increase of vascular permeability through a paracrine effect on VEGF in these subjects.

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 (the 1983 revision), and the Institutional Review Board of Tokyo Women's Medical University also approved the protocol for collection of vitreous fluid and blood samples. Vitreous fluid samples were

Vitreous levels of IL-6 and VEGF

Vitreous fluid protein levels (median [range]) were significantly higher in the diabetic subjects with DME than in the nondiabetic control subjects (3.12 mg/ml [0.55–8.42] vs. 0.55 mg/ml [0.21–2.42], P = 0.0008). The vitreous fluid concentration of VEGF was also significantly elevated in the subjects with DME (818.0 pg/ml [36.8–1902.4]) when compared with the control subjects (17.8 pg/ml [15.6–26.2], P<0.0001, Fig 1A). Furthermore, the VEGF/protein ratio showed a significant difference between

Discussion

In the present and previous studies,7, 8 we have shown that aqueous levels of both IL-6 and VEGF are correlated not only with the severity of diabetic retinopathy and the grade of fundus findings, such as retinal hemorrhages and hard exudates, but also with the severity of DME. We have also shown that the aqueous level of IL-6 is significantly correlated with that of VEGF.7, 8 Furthermore, both VEGF and IL-6 concentrations are higher in the aqueous humor than in the plasma.7, 8 Although it has

Acknowledgements

We thank Drs Shigehiko Kitano, Erika Shimizu, Hidetaka Noma, Yuichiro Nakanishi, Koji Makita, Kensuke Haruyama, and Shinko Nakamura for their assistance in collecting the vitreous and plasma samples and in performing the ophthalmological 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 (Department of Biostatistics, STATZ Institute Co., Ltd.) for his

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  • Cited by (0)

    Manuscript no. 220444.

    Supported by a Health Science Research Grant (#10060101 to Drs Funatsu, Hori, and Yamashita) from the Japanese Ministry of Health, Labor and Welfare (Tokyo, Japan).

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