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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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Eman A. Toraih

  2. Center of Excellence of Molecular and Cellular Medicine, Suez Canal University, Ismailia, Egypt

    Eman A. Toraih

  3. Department of Ophthalmology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Ahmed A. Abdelghany

  4. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Noha M Abd El Fadeal & Manal S. Fawzy

  5. Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, Saudi Arabia

    Essam Al Ageeli

  6. Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia

    Manal S. Fawzy

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  1. Eman A. Toraih
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Correspondence to Manal S. Fawzy.

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Toraih, E.A., Abdelghany, A.A., Abd El Fadeal, N.M. et al. 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. Graefes Arch Clin Exp Ophthalmol 257, 1897–1913 (2019). https://doi.org/10.1007/s00417-019-04409-9

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