Elevation of the vitreous body concentrations of oxidative stress-responsive apoptosis-inducing protein (ORAIP) in proliferative diabetic retinopathy

  • Yuta Suzuki
  • Takako Yao
  • Ko Okumura
  • Yoshinori SekoEmail author
  • Shigehiko Kitano
Medical Ophthalmology



Oxidative stress has been implicated in the pathogenesis of various disorders, including diabetic retinopathy (DR). Oxidative stress-responsive apoptosis-inducing protein (ORAIP; a tyrosine-sulfated secreted form of eukaryotic translation initiation factor 5A [eIF5A]) is a recently discovered pro-apoptotic ligand that is secreted from cells in response to oxidative stress and induces apoptosis in an autocrine fashion. This study aimed to determine if ORAIP plays a role in DR.


To investigate the role of ORAIP in DR, we analyzed the levels of ORAIP in the vitreous body and their relationship with the extent of proliferative diabetic retinopathy (PDR). Enzyme-linked immunosorbent assay was used to quantify the levels of ORAIP, vascular endothelial growth factor (VEGF), C–C motif chemokine ligand 2 (CCL2), interleukin-6 (IL-6), and IL-8 in the vitreous body of 40 eyes from 28 patients with PDR and 11 patients with non-PDR (NPDR). We also analyzed the expression of ORAIP in insoluble proliferative tissues from vitreous body samples by immunofluorescent staining.


The vitreous body concentration of ORAIP was significantly (P = 0.0433) higher in the PDR group (52.26 ± 8.68 [mean ± SE] ng/mL, n = 29) than in the NPDR group (28.21 ± 7.30 ng/mL, n = 11). However, there were no significant correlations between the concentration of ORAIP and those of VEGF, IL-6, CCL2, or IL-8. ORAIP expression was observed in the insoluble proliferative tissues in vitreous body samples of most patients in the PDR group, whereas almost no expression of ORAIP was observed in patients in the NPDR group.


Our findings strongly suggest that ORAIP plays a role in oxidative stress-induced retinal injury and may be a sensitive diagnostic marker and a promising therapeutic target for oxidative stress-induced cytotoxicity.


Chemokines Diabetic retinopathy Oxidative stress-responsive apoptosis inducing protein Proliferative diabetic retinopathy Vascular endothelial growth factor Vitreous body 



Editorial support in the form of medical writing was provided by Editage (, a division of Cactus Communications Pvt., Ltd.


This work was supported by a grant from Takeda Research Support and Novartis Pharma Research Grants and by research support from Alcon Pharma, Senju Pharmaceutical Co. Ltd. and Bayer Pharmaceutical Co., Ltd.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association and was approved by the Ethics Committee of Tokyo Women’s Medical University.

Informed consent

Informed written consent was obtained from all patients before ophthalmologic examination.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Ophthalmology, Diabetes CenterTokyo Women’s Medical UniversityTokyoJapan
  2. 2.Division of Cardiovascular Medicine, Institute for Adult DiseasesAsahi Life FoundationTokyoJapan
  3. 3.Department of Biofunctional Microbiota, Graduate School of MedicineJuntendo UniversityTokyoJapan

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