July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Changes in histone deacetylases (HDACs) in glaucomatous optic nerve.
Author Affiliations & Notes
  • Wendy Guzman
    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   Wendy Guzman, None; Sudha Singh, None; Shahid Husain, None
  • Footnotes
    Support  NIH EY-027355
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 30. doi:
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      Wendy Guzman, Sudha Singh, Shahid Husain; Changes in histone deacetylases (HDACs) in glaucomatous optic nerve.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):30.

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

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Abstract

Purpose : This study was designed to determine the changes in the levels of histone Deacetylase (HDACs) in glaucomatous optic nerve and their reversion by delta (δ) opioid receptor agonist (SNC-121) treatment in glaucoma rat model.

Methods : Brown Norway rats were used to elevate intraocular pressure (IOP) by injecting 50 microliter of 2M of hypertonic saline injection into circumferential limbal veins. Both male and female animals were treated with SNC-121 (1mg/kg., i.p.) daily for seven days. IOP was recorded weekly using a calibrated Tonolab tonometer. Pattern electroretinograms (ERGs) and optokinetic responses (OKR) were measured on day 0, 14 and 42 day, post injury. The optic nerves were analyze for HDAC expression by immunohistochemistry and Western Blotting.

Results : Intraocular pressure was increased significantly between 7-42 days, post injury. Pattern-ERGs and OKR were also significantly reduced in ocular hypertensive animals and they were reversed by SNC-121 treatment. The expression levels of HDAC-1, HDAC-2, HDAC-3 and HDAC-6 were increased by 2-6 folds in ocular hypertensive optic nerved when compared to normal optic nerves. Interestingly, the expression level of HDAC-1, HDAC-2 and HDAC-3 was drastically reduced in SNC-121 treated ocular hypertensive animals whereas HDAC-6 level was marginally affected by SNC-121 treatment.

Conclusions : Our data provides evidence that class 1 HDACs play crucial role in glaucoma pathology as they are up-regulated in response to ocular injury. Additionally we have shown that SNC-121 mediated retina neuroprotection could be due to attenuation in the up-regulation of class I HDACs in optic nerve.

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

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