July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Regulation of cytokines and STATs by delta opioid receptor activation in rat glaucoma model.
Author Affiliations & Notes
  • Syed A Zaidi
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • Sudha Singh
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • Shahid Husain
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • Footnotes
    Commercial Relationships   Syed Zaidi, None; Sudha Singh, None; Shahid Husain, None
  • Footnotes
    Support  NH Grant EY027355
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 37. doi:
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      Syed A Zaidi, Sudha Singh, Shahid Husain; Regulation of cytokines and STATs by delta opioid receptor activation in rat glaucoma model.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):37.

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

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Abstract

Purpose : The present study was designed to determine if δ-opioid receptor activation stabilizes acetylation homeostasis during glaucomatous injury.

Methods : Intraocular pressure (IOP) was elevated by injecting 2M hypertonic saline into the episcleral veins in the eyes of Brown Norway rats. SNC-121 was administered (1 mg/kg; i.p.) once a day for 7 days. Quantitative PCR array was used to measure transcription factors and cytokines in the retina at day 7, post-injury. Purified human optic nerve head (ONH) were treated with 1µM SNC-121 for 24 h. Changes in the HDACs expression and their activity was determined by Western blotting and enzyme assay kits, respectively.

Results : Elevated IOP resulted in a decrease in acetylated H3 levels (42.1±8 %; P<0.05) and increase in class I HDAC activity (20.1±5.2%; P<0.05) in the retina of ocular hypertensive animals, which were reversed by SNC-121 treatment. Quantitative RT-PCR array identified 29 out of 84 transcripts that were differentially expressed (>2 fold) in the retina of ocular hypertensive animals. Particularly, expression of IL-6 and IL-1β and transcriptional factor, STAT 1, 3, and 4 (> 2 fold; p<0.05) was increased in the ocular hypertensive animal. Interestingly, SNC-121 administration reversed the expression of pro-inflammatory cytokines and transcriptional factors. Additionally, SNC-121 treatment enhances H3 acetylation and reduces class I HDACs expression and enzyme activity in ONH astrocytes.

Conclusions : Our data suggest that SNC-121 alleviates acetylation and reduces HDAC activity in the retina and ONH astrocytes. Hypoacetylation of histones is often linked to pro-inflammatory cytokines production and RGC death. Our data suggest that SNC-121 suppresses pro-inflammatory cytokines and the expression of the transcription factors in the retina. These data provide new leads to investigate how cytokines and their transcription (e.g. ILs/STATs) contribute to RGC death and if it is counterbalanced by δ-opioid receptor activation.

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

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