July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Identification of a microRNA signature in the serum of non-infectious uveitis patients
Author Affiliations & Notes
  • Fleurieke H Verhagen
    Ophthalmology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Cornelis Bekker
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Marzia Rossato
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Sanne Hiddingh
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Lieuwe de Vries
    Ophthalmology, Radboud University Medical Center Nijmegen, Nijmegen, Netherlands
  • Abhinandan Devaprasad
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Aridaman Pandit
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Jeanette Ossewaarde-van Norel
    Ophthalmology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Ninette ten Dam-van Loon
    Ophthalmology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Maartje Moret-Pot
    Ophthalmology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Saskia Imhof
    Ophthalmology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Joke de Boer
    Ophthalmology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Timothy Radstake
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
    Rheuatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands
  • Jonas Kuiper
    Ophthalmology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
    Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
  • Footnotes
    Commercial Relationships   Fleurieke Verhagen, None; Cornelis Bekker, None; Marzia Rossato, None; Sanne Hiddingh, None; Lieuwe de Vries, None; Abhinandan Devaprasad, None; Aridaman Pandit, None; Jeanette Ossewaarde-van Norel, None; Ninette ten Dam-van Loon, None; Maartje Moret-Pot, None; Saskia Imhof, None; Joke de Boer, None; Timothy Radstake, None; Jonas Kuiper, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5380. doi:https://doi.org/
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      Fleurieke H Verhagen, Cornelis Bekker, Marzia Rossato, Sanne Hiddingh, Lieuwe de Vries, Abhinandan Devaprasad, Aridaman Pandit, Jeanette Ossewaarde-van Norel, Ninette ten Dam-van Loon, Maartje Moret-Pot, Saskia Imhof, Joke de Boer, Timothy Radstake, Jonas Kuiper; Identification of a microRNA signature in the serum of non-infectious uveitis patients
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):5380. doi: https://doi.org/.

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

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Abstract

Purpose : The cause of non-infectious uveitis (NIU) is poorly understood, but is considered to be mediated by a complex interplay between multiple genetic, epigenetic and environmental factors. MicroRNAs (miRNAs) are non-coding small RNAs that control gene translation into protein. MiRNAs have been shown to be critical mediators in several pathological and inflammatory processes.

Methods : To identify changes in circulating miRNA levels of patients with non-infectious uveitis compared with healthy controls, we exploited a high dimensional and multiple-level approach assessing and integrating the miRNA-ome and leukocyte composition in patients with NIU.
Serum was collected from 54 untreated patients with active and eye-restricted disease and compared with 26 age-matched controls distributed over 2 independent cohorts. TaqMan OpenArray sequencing technology was used to screen for 753 miRNAs in serum in the first cohort. TaqMan single quantitative reverse transcription PCR (RT-qPCR) was used to validate the findings in a second, independent, cohort. Paired flow cytometry results were integrated with the miRNA data to study the relationship between miRNAs and leukocyte composition.

Results : Using stringent selection criteria we identified and independently validated a NIU associated miRNA cluster consisting of seven microRNAs. Pathway enrichment analysis for genes targeted by these miRNAs revealed significant enrichment for the PI3K/Akt, MAPK, FOXO and VEGF signaling pathways as well as for photoreceptor development; all considered to be central pathways for various inflammatory eye conditions. In addition, high dimensional multi-level analysis of the miRNA cluster - guided by proteome and cytome data - linked the presence of the NIU-associated miRNA cluster to a different composition of leukocyte subsets, more specifically CD16+lindimCD11c+HLA-DR- cells, in these patients.

Conclusions : Together, this study identifies a unique miRNA cluster associated with non-infectious uveitis and describes a novel approach to map circulating miRNAs to leukocyte subsets. Furthermore, our data refute the prevailing paradigm that uveitis does not go beyond the eye by demonstrating systemic changes in epigenetic regulation underlying non-infectious uveitis.

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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