July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
DNA Methylation of human trabecular meshwork: searching for biomarkers of glaucoma
Author Affiliations & Notes
  • Vicente Zanon-Moreno
    Area of Health Sciences, Valencian International University - VIU, Valencia, Valencia, Spain
  • Silvia Maria Sanz-Gonzalez
    Ophthalmology Research Unir "Santiago Grisolia", FISABIO, Valencia, Valencia, Spain
    Thematic Network of Cooperative Research in Ocular Pathology (OFTARED), Carlos III Health Institute, Valencia, Valencia, Spain
  • Jose Javier Garcia-Medina
    Department of Ophthalmology, Morales Meseguer University General Hospital, Murcia, Murcia, Spain
    Thematic Network of Cooperative Research in Ocular Pathology (OFTARED), Carlos III Health Institute, Valencia, Valencia, Spain
  • Maria D Pinazo-Duran
    Ophthalmology Research Unir "Santiago Grisolia", FISABIO, Valencia, Valencia, Spain
    Thematic Network of Cooperative Research in Ocular Pathology (OFTARED), Carlos III Health Institute, Valencia, Valencia, Spain
  • Oscar Coltell
    Department of Computer Languages and Systems, Universitat Jaume I, Castellón, Castellón, Spain
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
  • Dolores Corella
    Department of Preventive Medicine & Public Health, University of Valencia, Valencia, Valencia, Spain
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
  • Footnotes
    Commercial Relationships   Vicente Zanon-Moreno, None; Silvia Sanz-Gonzalez, None; Jose Javier Garcia-Medina, None; Maria Pinazo-Duran, None; Oscar Coltell, None; Dolores Corella, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6071. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Vicente Zanon-Moreno, Silvia Maria Sanz-Gonzalez, Jose Javier Garcia-Medina, Maria D Pinazo-Duran, Oscar Coltell, Dolores Corella; DNA Methylation of human trabecular meshwork: searching for biomarkers of glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6071.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To study the DNA methylation status of patients with primary open-angle glaucoma (POAG), and the expression of genes hypo- or hypermethylated and the concentration of the proteins coded by those genes in POAG.

Methods : A case-control study in POAG patients and control subjects was carried out. First, we performed the study of the DNA methylation in trabecular meshwork samples of POAG patients (n=15) and cadaver samples (n=15), combining bisulfite conversion of genomic DNA and whole-genome amplification. After that, we analyzed the relative expression of several hypo- and hypermethylated genes in blood samples of POAG patients (n=30) and healthy controls (n=30) by real time PCR (7900HT Fast Real-Time PCR System, Applied Biosystems, Foster City, CA, USA). Finally, we determined the concentration of the proteins coded by those genes by means of enzyme-linked immunosorbent assays.

Results : After sequencing the samples, we got the methylation status of thousand genes and loci. Among them, the TP53AIP1, VSX2 and CDH23 genes were hypomethylated and the GPX4, GDNF and PITX1 genes were hypermethylated in POAG samples compared to control samples. The hypomethylated genes showed a higher expression in the POAG group, but only the difference in expression of the TP53AIP1 gene was statistically significant (p=0.001). Regarding the hypermethylated genes, only the GPX4 gene had a significantly lower expression in POAG group (p=0.025). We observed statistically significant differences in the concentration of proteins encoded by the genes with differential expression between POAG and control groups (TP53AIP1 and GPX4).

Conclusions : The DNA methylation profile is different in trabecular meshwork of primary open-angle glaucoma compared to controls. Due to the different methylation status, the expression of the TP53AIP1 gene and the protein encoded by this gene is increased and GPX4 gene and its protein is decreased in POAG. Thus, apoptosis in trabecular meshwork is stimulated while the antioxidant capacity is inhibited in the glaucoma group. Further studies in larger sample sizes are needed to clarify the role of epigenetic alterations in the onset and / or progression of glaucomatous disease.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×