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