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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.
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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.
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.
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.
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.
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