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ELEVATION OF ANGIOGENIC FACTOR CYSTEINE-RICH 61 LEVELS IN VITREOUS OF PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY

You, Jian Jang MD, PhD*†; Yang, Chung May MD; Chen, Muh Shy MD, PhD; Yang, Chang-Hao MD, PhD

doi: 10.1097/IAE.0b013e318219e4ad
Original Study
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Purpose: Cysteine-rich 61 (Cyr61) is one of the angiogenic factors involved in proliferative diabetic retinopathy (PDR). To further investigate its role, we measure and compare the vitreous levels of Cyr61 and vascular endothelial growth factor in patients with PDR and to localize Cyr61 expression in associated proliferative epiretinal membranes.

Methods: Vitreous obtained from 56 patients with active PDR, 16 patients with active PDR pretreated with bevacizumab, 19 patients with quiescent PDR, 15 non–PDR patients with diabetic macular edema, and 25 patients with non–diabetic-related eye diseases were subjected to enzyme-linked immunosorbent assay for Cyr61 and vascular endothelial growth factor levels. Epiretinal membranes from 18 patients were stained immunohistochemically for Cyr61.

Results: Vitreous Cyr61 levels were significantly higher in active PDR patients, quiescent PDR patients, and diabetic macular edema patients compared with non–diabetic control patients (P < 0.01). Pretreatment of bevacizumab significantly suppressed vitreous vascular endothelial growth factor levels; however, it did not inhibit vitreous Cyr61 levels in active PDR patients. Cysteine-rich 61 was strongly detected in endothelial cells and myofibroblasts within active PDR membranes but not in idiopathic epiretinal membrane.

Conclusion: Vitreous Cyr61 levels were related to different states of PDR and correlated with vascular endothelial growth factor levels in PDR patients. Pretreatment of bevacizumab did not inhibit vitreous Cyr61 levels in active PDR patients. Cysteine-rich 61 might mediate angiogenesis and post-angiogenic fibrosis in PDR.

A retrospective case–control study showed that vitreous levels of cysteine-rich 61, an angiogenic factor, were significantly elevated in active proliferative diabetic retinopathy and could not be inhibited by pretreatment with bevacizumab. Cysteine-rich 61 was strongly detected in endothelial cells and myofibroblasts within active proliferative diabetic retinopathy membranes but not in idiopathic epiretinal membrane. It might mediate angiogenesis and post-angiogenesis fibrosis.

From the *Department of Ophthalmology, Keelung General Hospital, Department of Health, the Executive Yuan, Keelung, Taiwan; †Ching-Kuo Institute of Management and Health, Keelung, Taiwan; and ‡Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.

The authors have no financial interest or conflicts of interest.

Supported by grant NSC 96-2628-B-002-032-MY3 from the National Science Council, Executive Yuan, Republic of China (to C.M.Y. and C.-H.Y.), from the National Taiwan University Hospital (to C.-H.Y.), and from grant 9816 from the Keelung General Hospital, Department of Health, the Executive Yuan, Keelung, Republic of China (to J.J.Y.).

Reprint requests: Chang-Hao Yang, MD, PhD, Department of Ophthalmology, National Taiwan University Hospital, No. 7, Chung-Shan S Road, Taipei, Taiwan; e-mail: chyangoph@ntu.edu.tw

© The Ophthalmic Communications Society, Inc.