Changes in class I and IIb HDACs by δ-opioid in chronic rat glaucoma model

Syed A.H. Zaidi, Wendy Guzman, Sudha Singh, Shikhar Mehrotra, Shahid Husain

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

PURPOSE. This study determines if δ-opioid receptor agonist (i.e. SNC-121)-induced epigenetic changes via regulation of histone deacetylases (HDACs) for retinal ganglion cell (RGC) neuroprotection in glaucoma model. METHODS. Intraocular pressure was raised in rat eyes by injecting 2M hypertonic saline into the limbal veins. SNC-121 (1 mg/kg; i.p.) was administered to the animals for 7 days. Retinas were collected at days 7 and 42, post-injury followed by measurement of HDAC activities, mRNA, and protein expression by enzyme assay, quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry. RESULTS. The visual acuity, contrast sensitivity, and pattern electroretinograms (ERGs) were declined in ocular hypertensive animals, which were significantly improved by SNC-121 treatment. Class I and IIb HDACs activities were significantly increased at days 7 and 42 in ocular hypertensive animals. The mRNA and protein expression of HDAC 1 was increased by 1.33 ± 0.07-fold and 20.2 ± 2.7%, HDAC 2 by 1.4 ± 0.05-fold and 17.0 ± 2.4%, HDAC 3 by 1.4 ± 0.06-fold and 17.4 ± 3.4%, and HDAC 6 by 1.5 ± 0.09-fold and 15.1 ± 3.3% at day 7, post-injury. Both the mRNA and protein expression of HDACs were potentiated further at day 42 in ocular hypertensive animals. HDAC activities, mRNA, and protein expression were blocked by SNC-121 treatment at days 7 and 42 in ocular hypertensive animals. CONCLUSIONS. Data suggests that class I and IIb HDACs are activated and upregulated during early stages of glaucoma. Early intervention with δ-opioid receptor activation resulted in the prolonged suppression of class I and IIb HDACs activities and expression, which may, in part, play a crucial role in RGC neuroprotection.

Original languageEnglish (US)
Article number:4
JournalInvestigative Ophthalmology and Visual Science
Volume61
Issue number14
DOIs
StatePublished - Dec 2020
Externally publishedYes

Keywords

  • Epigenetics
  • Glaucoma
  • HDACs
  • Neuroprotection
  • Opioids

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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