July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Novel Biomarker for diagnosis, prognosis, and targeted therapy of Keratoconus
Author Affiliations & Notes
  • Rabab Sharif
    University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Sashia Bak-Nielsen
    Aarhus University Hospital, Aarhus, Denmark
  • Henrik Sejersen
    Aarhus University Hospital, Aarhus, Denmark
  • Jesper Hjortdal
    Aarhus University Hospital, Aarhus, Denmark
  • Dimitrios Karamichos
    University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Rabab Sharif, None; Sashia Bak-Nielsen, None; Henrik Sejersen, None; Jesper Hjortdal, None; Dimitrios Karamichos, None
  • Footnotes
    Support  NIH/NEI EY023568
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 742. doi:
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      Rabab Sharif, Sashia Bak-Nielsen, Henrik Sejersen, Jesper Hjortdal, Dimitrios Karamichos; Novel Biomarker for diagnosis, prognosis, and targeted therapy of Keratoconus. Invest. Ophthalmol. Vis. Sci. 2018;59(9):742.

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

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Abstract

Purpose : Keratoconus (KC) is a corneal disease of complex etiology, where differentiation between association, cause, and effect is challenging and varies between individuals. Currently, there is no animal model to assist in the deeper understanding of KC pathobiology. Thus, the exact etiology of KC remains unclear. In our study, we identified significant hormonal imbalance in KC patients that were tightly linked to the expression and modulation of a proposed biomarker; Prolactin-Induced Protein (PIP).This is the first comprehensive study of its kind.

Methods : Saliva, tears, and serum samples were collected from 160 KC patients, of which 111 (69.4%) were male and 49 (30.6%) were female patients. In addition, 30 healthy controls were included, of which 18 (60%) were female and 12 (40%) were male. All samples were aged-matched with an average age of 34 years old in both KC patients and healthy controls. KC patients were mid-moderate stage in severity. Data analysis was performed using western blots and enzyme-linked immunosorbent assays.

Results : We analyzed hormone levels based on gender, in order to determine differences between KC patients and healthy controls. Our data showed a significant upregulation in salivary DHEA-S levels (p< 0.0001), independent of gender. Furthermore, data revealed a significant downregulation of both estrone and estriol levels in KC patients compared to healthy controls (p< 0.0001, p< 0.05; respectively). Female-dependent elevation in both estrone and estriol was detected compared to their male counterparts.Levels of 17β-estradiol in KC patients compared to healthy controls were non-significant, independent of gender. PIP protein expression level was significantly downregulated in all KC saliva (p< 0.001), tears (p<0.0001), and serum (p<0.001), compared to healthy controls, and independent of gender.

Conclusions : Our study shows that reduction in estrogen-based hormones and increase in androgen-based hormones, in correlation with reduced PIP levels in the human KC, may significantly alter the corneal homeostasis and exacerbate the underlying KC-corneal thinning. Hormone-PIP interdependency highlights the potential of PIP as the first KC biomarker.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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