June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Vitamin C contributes to epigenetic regulation of genes related to diabetic retinopathy in retinal endothelial cells
Author Affiliations & Notes
  • Walker Kay
    Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, Utah, United States
  • Jonathon Reynolds
    Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, Utah, United States
  • Elizabeth Turner
    Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, Utah, United States
  • Marianne Becnel
    Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, Utah, United States
  • Gaofeng Wang
    Department of Human Genetics, University of Miami School of Medicine, Miami, Florida, United States
  • David Sant
    Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, Utah, United States
  • Footnotes
    Commercial Relationships   Walker Kay None; Jonathon Reynolds None; Elizabeth Turner None; Marianne Becnel None; Gaofeng Wang None; David Sant None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 995. doi:
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    • Get Citation

      Walker Kay, Jonathon Reynolds, Elizabeth Turner, Marianne Becnel, Gaofeng Wang, David Sant; Vitamin C contributes to epigenetic regulation of genes related to diabetic retinopathy in retinal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2023;64(8):995.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glucose acts as a competitive inhibitor for the transport of vitamin C (ascorbate) across the blood retinal barrier (BRB). In addition to acting as a reducing agent, vitamin C acts as a cofactor for the TET enzymes. High glucose levels in hyperglycemia inhibit the transport of vitamin C across the BRB and lead to a local deficiency in the eyes of diabetics, and this local deficiency leads to impaired DNA methylation-demethylation dynamics. We hypothesize that impaired function of the TET enzymes leads to changes in transcription in the retina, which contribute to pathologic changes that contribute to diabetic retinopathy.

Methods : Primary, human retinal endothelial cells were cultured in 15.7 mM glucose (283 mg/dL) either in the presence or absence of vitamin C (50 µm) for five days. Immunohistochemistry, whole-transcriptome sequencing, and qPCR were used to determine and verify changes.

Results : After treatment with vitamin C, there was a global increase in hydroxymethylcytosine, consistent with previous reports. RNA-seq revealed that 437 genes were found to have upregulated transcription and 308 genes were found to have downregulated transcription. Pathway analysis highlighted changes in several pathways that may elucidate changes that occur in retinal endothelial cells that contribute to the pathogenesis of diabetic retinopathy. Genes related to Insulin-like growth factor 1 (IGF-1) signaling and VEGFA-VEGFR2 signaling exhibited reduced transcription after treatment with vitamin C. Additionally, pathways related to leukocyte adhesion to endothelial cells were downregulated. GWAS studies have shown that mutations in one specific leukocyte adhesion gene, SELP, which codes for P-selectin, are correlated with diabetic retinopathy. A downregulation in SELP after vitamin C treatment was confirmed by qPCR.

Conclusions : These data suggest that local vitamin c deficiencies in the eyes of diabetics affect signaling in the retinal endothelial cells which may contribute to the breakdown of the blood-retinal barrier in diabetic retinopathy.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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