Deciphering the role of circulating lncRNAs: RNCR2, NEAT2, CDKN2B-AS1, and PVT1 and the possible prediction of anti-VEGF treatment outcomes in diabetic retinopathy patients

  • Eman A. Toraih
  • Ahmed A. Abdelghany
  • Noha M Abd El Fadeal
  • Essam Al Ageeli
  • Manal S. FawzyEmail author
Basic Science



Putative roles of long non-coding RNAs (lncRNAs) as indicators for diabetic retinopathy (DR) and associated complications are beginning to emerge. We aimed to evaluate a panel of circulating hyperglycemia-related lncRNAs: RNCR2, NEAT2, CDKN2B-AS1, and PVT1 in type 2 diabetes patients with/without DR and to correlate their levels with the clinical characteristics and response to aflibercept intravitreal injection in terms of visual acuity (VA) improvement, central macular thickness (CMT) decline, and macular edema resolution after 4 weeks of the initial injection.


Pre-treatment plasma relative expression levels of the specified lncRNAs were quantified in 130 consecutive patients with diabetes (75 and 55 with/without DR, respectively) and 108 controls using quantitative real-time PCR.


One month after aflibercept injection, significant reductions in CMT and VA were observed in DR cohorts. The four lncRNAs were over-expressed in DM compared with those in controls. However, downregulated baseline plasma levels of RNCR2 and NEAT2 were observed in glycemic-controlled DR patients. None of the lncRNAs showed a correlation with the severity of retinopathy or drug response.


Though circulating levels of the analyzed lncRNAs did not show an association with DR progression or aflibercept therapy response, the expression pattern demonstrated good diagnostic performance in differentiating DM from controls and DR.


Anti-VEGF Biomarker Diabetic retinopathy Gene expression Long non-coding RNAs RNCR2 NEAT2 CDKN2B-AS1 PVT1 qRT-PCR 



The authors thank the Center of Excellence in Molecular and Cellular Medicine and the Oncology Diagnostic Unit, Suez Canal University, Ismailia, Egypt, for providing the facilities for performing the molecular work of the current study. The authors also thank all the participants for their approval to join this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

417_2019_4409_MOESM1_ESM.docx (1.5 mb)
ESM 1 (DOCX 1516 kb)
417_2019_4409_MOESM2_ESM.docx (33 kb)
ESM 2 (DOCX 33 kb)


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Copyright information

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

Authors and Affiliations

  1. 1.Genetics Unit, Department of Histology and Cell Biology, Faculty of MedicineSuez Canal UniversityIsmailiaEgypt
  2. 2.Center of Excellence of Molecular and Cellular MedicineSuez Canal UniversityIsmailiaEgypt
  3. 3.Department of Ophthalmology, Faculty of MedicineSuez Canal UniversityIsmailiaEgypt
  4. 4.Department of Medical Biochemistry and Molecular Biology, Faculty of MedicineSuez Canal UniversityIsmailiaEgypt
  5. 5.Department of Clinical Biochemistry (Medical Genetics), Faculty of MedicineJazan UniversityJazanSaudi Arabia
  6. 6.Department of Biochemistry, Faculty of MedicineNorthern Border UniversityArarSaudi Arabia

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