Increased concentration of pentosidine, an advanced glycation end product, and interleukin-6 in the vitreous of patients with proliferative diabetic retinopathy

Nakamura, Naoto; Hasegawa, Goji; Obayashi, Hiroshi; Yamazaki, Masahiro; Ogata, Masakazu; Nakano, Koji; Yoshikawa, Toshikazu; Watanabe, Akihide; Kinoshita, Shigeru; Fujinami, Aya; Ohta, Mitsuhiro; Imamura, Yutaka; Ikeda, Tsunehiko

doi:10.1016/S0168-8227(03)00109-8

« Previous Next »Diabetes Research and Clinical Practice
Volume 61, Issue 2 , Pages 93-101, August 2003

Increased concentration of pentosidine, an advanced glycation end product, and interleukin-6 in the vitreous of patients with proliferative diabetic retinopathy

Naoto Nakamura
- First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan
- Corresponding author. Tel.: +81-75-251-5505; fax: +81-75-252-3721
Goji Hasegawa
- First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan
Hiroshi Obayashi
- First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan
Masahiro Yamazaki
- First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan
Masakazu Ogata
- First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan
Koji Nakano
- First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan
Toshikazu Yoshikawa
- First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan
Akihide Watanabe
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Shigeru Kinoshita
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Aya Fujinami
- Department of Clinical Chemistry, Kobe Pharmaceutical University, Kobe, Japan
Mitsuhiro Ohta
- Department of Clinical Chemistry, Kobe Pharmaceutical University, Kobe, Japan
Yutaka Imamura
- Department of Ophthalmology, Osaka Medical College, Osaka, Japan
Tsunehiko Ikeda
- Department of Ophthalmology, Osaka Medical College, Osaka, Japan

Received 6 January 2003; received in revised form 1 April 2003; accepted 16 April 2003.

Abstract

To investigate the relationship between advanced glycation end products (AGEs) and interleukin-6 (IL-6) in the development of diabetic retinopathy, we determined the concentrations of pentosidine, a well-characterized AGE, and IL-6 in the vitreous of 62 patients with proliferative diabetic retinopathy (PDR) and 50 non-diabetic control subjects. We also investigated the effect of AGEs on the production of IL-6 by human retinal Müller cells. The levels of pentosidine and IL-6 in the vitreous of patients with PDR were significantly higher compared with controls. In patients with PDR with vitreous hemorrhage (VH), the mean vitreous concentration of IL-6 was significantly higher than that in PDR patients without VH. There was a strong positive correlation between the vitreous levels of pentosidine and IL-6. Levels of IL-6 were strikingly higher in the vitreous compared with the serum and there was no correlation between IL-6 concentrations in the two fluids. Treatment of Müller cells with AGEs for 48 h resulted in a dose-dependent increase of IL-6 in the culture medium. These results suggest that increased formation of AGEs in the vitreous may be involved in the development of diabetic retinopathy by inducing the production of IL-6 from retinal Müller cells.

Keywords: Diabetic retinopathy, Advanced glycation end products, Interleukin-6, Vitreous, Retinal Müller cell

Abbreviations: AGE(s), advanced glycation end products, BSA, bovine serum albumin, ELISA, enzyme-linked immunosorbent assay, IL-6, interleukin-6, PDR, proliferative diabetic retinopathy, TRD, tractional retinal detachment, VEGF, vascular endothelial growth factor, VH, vitreous hemorrhage