September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The role of the interleukin-20 (IL-20) family of cytokines and receptors in the normal and glaucomatous aqueous outflow pathway
Author Affiliations & Notes
  • Mary Wirtz
    Ophthalmology, Oregon Health & Sciences University, Portland, Oregon, United States
  • Renee Sykes
    Ophthalmology, Oregon Health & Sciences University, Portland, Oregon, United States
  • Ying Ying Sun
    Ophthalmology, Oregon Health & Sciences University, Portland, Oregon, United States
  • Yong-feng Yang
    Ophthalmology, Oregon Health & Sciences University, Portland, Oregon, United States
  • Kate E Keller
    Ophthalmology, Oregon Health & Sciences University, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Mary Wirtz, None; Renee Sykes, None; Ying Ying Sun, None; Yong-feng Yang, None; Kate Keller, None
  • Footnotes
    Support  NIH grant EY011650 (MKW), NIH grant P30 EY010572 (MKW), NIH grant EY019643 (KEK), a Sybil B. Harrington Special Scholar Award (KEK) and an unrestricted grant from Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6016. doi:
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    • Get Citation

      Mary Wirtz, Renee Sykes, Ying Ying Sun, Yong-feng Yang, Kate E Keller; The role of the interleukin-20 (IL-20) family of cytokines and receptors in the normal and glaucomatous aqueous outflow pathway. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6016.

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

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Abstract

Purpose : The IL-20 subfamily of cytokines and receptors includes cytokines IL-19, IL-20 and IL-24 and the receptors IL-20RA and IL-20RB, which function in both inflammatory and anti-inflammatory responses. We recently identified a T104M mutation in interleukin-20 receptor-B (IL-20RB) in primary open-angle glaucoma patients from a large pedigree. In this study, our goal was to determine the role of the IL-20 family of signaling molecules in the normal aqueous humor outflow pathway and dysfunction in glaucoma cells.

Methods : Western blot analysis and RT-PCR were used to look at expression of the IL-20 family members in trabecular meshwork (TM) cells. An ELISA assay was used to quantitate IL-20 and IL-19 in TM cells that were subject to mechanical stretch, an in vitro method that simulates the stretch/distortion placed on TM cells by elevated intraocular pressure. Porcine anterior perfusion cultures were treated with IL-19, IL-20 or IL-24 and outflow rates were measured for 72 hours. Signal Transducer and Activator of Transcription (STAT)-3 and generic matrix metalloproteinase (MMP) activity were evaluated in fibroblasts with the T104M IL-20RB mutation compared to wild-type fibroblasts.

Results : The IL-20 receptors (IL-20RA and IL20-RB) and IL-20 were expressed in trabecular meshwork cells. By ELISA, IL-20 protein levels in cultured trabecular meshwork cells significantly increased in response to stretch, but IL-19 was not detected. Flow rates in porcine anterior perfusion culture were significantly increased in response to IL-20, but not to IL-19 or IL-24. Stimulation of the IL-20RB receptor with IL-20 resulted in abnormal STAT3 activation and MMP activity in dermal fibroblasts from glaucoma patients with the T104M mutation compared to normal wild-type fibroblasts.

Conclusions : Our results demonstrate that IL-20 may be up-regulated in response to elevated intraocular pressure, which would in turn increase aqueous outflow via the conventional outflow pathway. In glaucoma patients with the IL-20RB mutation, disruption of normal IL-20 signaling in the trabecular meshwork may contribute to the degenerative processes associated with elevated intraocular pressure.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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