July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Role of hypoxia-inducible factor-1α (HIF-1α) in retinal ganglion cell (RGC) death in glaucoma.
Author Affiliations & Notes
  • 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   Sudha Singh, None; Shahid Husain, None
  • Footnotes
    Support  EY-027355
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 22. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sudha Singh, Shahid Husain; Role of hypoxia-inducible factor-1α (HIF-1α) in retinal ganglion cell (RGC) death in glaucoma.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):22.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : This study was designed to determine the role of transcriptional factor, hypoxia-inducible factor-1α (HIF-1α), in retinal ganglion cell (RGC) death in chronic rat glaucoma model.

Methods : Brown Norway rats were used to elevate intraocular pressure (IOP) by injecting 50 µL of 2 M hypertonic saline into the circumferential limbal veins. IOP was recorded prior to surgery (baseline IOP) and weekly after injury. HIF-1α inhibitor (KC7F2; 0.05- 2 mg/kg; i.p.) was administered right after injury and subsequently daily for 28 days. Pattern-ERGs were recorded at 14 and 28 days, post injury. The changes in the level of pro-inflammatory cytokines were measured by RT-PCR, Western blotting, and immunohistochemistry.

Results : IOP was elevated and pattern-ERGs were declined in ocular hypertensive animals significantly (P<0.05) at day 28, and declined Pattern-ERGs were reversed in HIF-1α inhibitor treated animals. However, patter-ERGs were not changed at day 7 post injury, while HIF-1α was increased by 51±15 (P<0.05) in the retina and 75±7 (P<0.05) in the optic nerve of ocular hypertensive animals. Additionally, pro-inflammatory cytokines (e.g. TNF-α, and IL-1β) were up-regulated in ocular hypertensive animals at day 7 and 28, post injury and their levels were reduced in HIF-1α inhibitor treated animals.

Conclusions : Our data suggest that under glaucomatous injury hypoxic microenvironments develop not only in RGCs but also in optic nerve which will lead to the production of pro-inflammatory cytokines. Regulation of transcriptional factors like HIF-1α at an early stage of glaucoma can be a potential therapeutic strategy to cure this disease.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×