April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Molecular Biomarkers in Ocular Graft vs Host Disease (GVHD)-Associated Dry Eye (DE)
Author Affiliations & Notes
  • Lidia Cocho
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
  • Veronica Martinez
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
  • Maria-Jesus J. Gonzalez
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    CIBER-BBN (Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Itziar Fernández
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    CIBER-BBN (Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Carmen García-Vázquez
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
  • Michael E Stern
    Biological Sciences, Allergan Inc, Irvine, CA, CA
  • Margarita Calonge
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    CIBER-BBN (Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Amalia Enriquez-De-Salamanca
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    CIBER-BBN (Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Footnotes
    Commercial Relationships Lidia Cocho, None; Veronica Martinez, None; Maria-Jesus Gonzalez, None; Itziar Fernández, None; Carmen García-Vázquez, None; Michael Stern, Allergan (E); Margarita Calonge, Allergan (C); Amalia Enriquez-De-Salamanca, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2020. doi:
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    • Get Citation

      Lidia Cocho, Veronica Martinez, Maria-Jesus J. Gonzalez, Itziar Fernández, Carmen García-Vázquez, Michael E Stern, Margarita Calonge, Amalia Enriquez-De-Salamanca; Molecular Biomarkers in Ocular Graft vs Host Disease (GVHD)-Associated Dry Eye (DE). Invest. Ophthalmol. Vis. Sci. 2014;55(13):2020.

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

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Abstract

Purpose: To measure a panel of tear cytokines/chemokines and mRNA expression of inflammatory molecules in conjunctival epithelial cells in graft vs host disease (GVHD)-associated dry-eye (DE) patients and to correlate them with clinical features.

Methods: Ten GVHD-DE patients and 10 age and sex-related controls were evaluated. Patients were medically controlled and had discontinued eyedrops (except artificial tears) 7 days prior evaluation. OSDI questionnaire and clinical tests (conjunctival hyperemia, corneal and conjunctival staining, Schirmer test and tear break-up time) were performed. Unstimulated tears (1 ul) were collected from most symptomatic eye. Levels of EGF, IL-1RA, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IP-10/CXCL10, eotaxin 1/CCL11, IFN-γ, VEGF, TNF-α and RANTES were measured by multiplex bead assay and correlated with clinical parameters. Upper-bulbar conjunctival epithelial cells were collected by impression cytology and gene expression of 84 inflammatory molecules was determined by qRT2-PCR.

Results: EGF, IL-2 and IP-10/CXCL10 tear levels were decreased in GVHD-DE patients compared to controls (p=0.0009, p=0.028 and p=0.0002, respectively), whereas IFN-γ and IL-12p70 tear levels were increased (p=0.013 and p=0.014). In GVHD-DE patients IL-12p70 tear levels correlated positively with fluorescein corneal staining (rho=0.719, IC=0.1603, 0.9651) and negatively with Schirmer test score (rho=-0.7438, IC=-0.961,-0.1367). IP-10 showed a negative correlation with hyperemia (rho=-0.6005, IC=-0.9057,-0.0478). IFN-γ and IL-1RA levels correlated negatively with Schirmer test score (rho=-0.7438, IC=-0.961,-0.1367, and rho=-0.6781, IC=-0.9608,-0.1115, respectively). Thirty three out of the 84 genes analyzed in conjunctival epithelial cells had statistically significant different expression: IFN-γ, CCL18, IL-9, and CCL2 were highly increased (>15 fold), 26 genes were moderately upregulated (4-15 fold), whereas EGFR mRNA was downregulated (3.36 fold), all in GVHD-DE samples compared to controls.

Conclusions: Several molecules have shown to be increased and decreased in tears of GVHD-DE patients and to be differently expressed in conjunctival epithelial cells. Particularly EGF/EGFR and IFN-γ seem the most relevant molecules/genes to focus on in future studies. These results add further knowledge to the search for potential biomarkers in GVHD-DE.

Keywords: 474 conjunctiva • 490 cytokines/chemokines • 557 inflammation  
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