CORRELATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR WITH CHEMOKINES IN THE VITREOUS IN DIABETIC RETINOPATHY YOSHIHIRO WAKABAYASHI, MD,* YOSHIHIKO USUI, MD,† YOKO OKUNUKI, MD,† TAKESHI KEZUKA, MD,† MASARU TAKEUCHI, MD,† HIROSHI GOTO, MD,† TAKUYA IWASAKI, MD† Purpose: The purpose of this study was to simultaneously measure the concentrations of multiple cytokines, including vascular endothelial growth factor, in the vitreous of patients with diabetic retinopathy and to examine their relation with clinical findings. Methods: Vitreous samples from 46 eyes with diabetic retinopathy and 19 eyes with nondiabetic macular disease (controls) were used. Nine cytokines were simultaneously measured using a FACSCalibur flow cytometer. Results: Vascular endothelial growth factor, interleukin-8, monocyte chemotactic pro- tein-1, interferon-inducible protein-10, and monokine induced by interferon- were de- tected in the vitreous samples, and the concentrations were significantly (P  0.001) higher in patients with diabetic retinopathy compared with control subjects. Vascular endothelial growth factor, interleukin-8, monocyte chemotactic protein-1, and monokine induced by interferon- concentrations were significantly (P  0.05) higher in active retinopathy than in inactive retinopathy. Furthermore, a significant (P  0.01) positive correlation was observed between vascular endothelial growth factor concentration and interleukin-8, monocyte chemotactic protein-1, interferon-inducible protein-10, or monokine induced by interferon- concentration in the vitreous. Conclusion: Vascular endothelial growth factor, interleukin-8, monocyte chemotactic protein-1, interferon-inducible protein-10, and monokine induced by interferon- were expressed at high levels locally in ocular tissues in diabetic retinopathy, and these cyto- kines may form a network and interact to impact the pathogenesis of the disease. RETINA 30:339 –344, 2010 M any growth factors and cytokines, including chemokines, are involved in the onset and pro- gression of diabetic retinopathy (DR). Vascular endo- thelial growth factor (VEGF), a potent angiogenic factor, is expressed at high levels in the retina of patients with diabetes, resulting in a marked increase in its concentration in the vitreous. 1–3 Vascular endo- thelial growth factor is known to induce chemokines such as monocyte chemotactic protein-1 (MCP-1) 4 and interleukin (IL)-8. 5 These inflammatory factors promote migration of leukocytes and adhesion of leu- kocytes to vascular endothelial cells, resulting in in- creased vascular permeability and neovascularization, which leads to onset and progression of DR. There- fore, it is speculated that many cytokines act in a complementary manner and interact with each other to form a network in DR. Although previous studies have detected a number of cytokines from the vitreous of patients with DR, simultaneous detection of multiple cytokines from the same samples and analysis of their relation are rarely reported. In this study, we simultaneously measured multiple cytokines, including VEGF and chemo- kines, in the vitreous of eyes with DR and examined the relationship of cytokine expression with clinical findings as well as the interrelationship between the cytokines. From the *Department of Ophthalmology, Hachiouji Medical Center of Tokyo Medical University, Tokyo, Japan; and †Depart- ment of Ophthalmology, Tokyo Medical University, Tokyo, Japan. The first three authors contributed equally to this study. Reprint requests: Yoshihiro Wakabayashi, MD, Department of Ophthalmology, Hachiouji Medical Center of Tokyo Medical Uni- versity, 1163 Tate-machi, Hachiouji city, Tokyo 193-8639, Japan; e-mail: wbaki@tokyo-med.ac.jp 339