Activation of Nrf2/HO-1 pathway protects retinal ganglion cells from a rat chronic ocular hypertension model of glaucoma
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The objective of this work was to find out the effects of nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1) pathway on retinal ganglion cell (RGC) injury in glaucoma.
The chronic ocular hypertension (COH) rat models of glaucoma were constructed, and intraocular pressure (IOP) and RGC numbers were detected at different time points. Additionally, rats were divided into normal group (normal control rats), model group (COH model rats), and model + tBHQ group (COH model rats treated with Nrf activator, tBHQ). RGC apoptosis was detected by using TUNEL staining, and the expressions of Nrf2/HO-1 were detected by qRT-PCR and western blotting.
COH model rats showed significant IOP elevation and the increased mRNA and protein expressions of Nrf2 and HO-1 from 1 to 6 weeks after operation, with the evidently decreased RGC numbers at 4 weeks and 6 weeks after operation (all P < 0.05). Besides, rats in the model group had increased apoptosis index (AI) of RGCs and the elevated mRNA and protein expressions of Nrf2/HO-1 with remarkably reduced RGC numbers when compared with normal control rats, but the model rats treated with tBHQ exhibited an apparent decrease in AI of RGCs, as well as remarkable increases in RGC numbers and the mRNA and protein expression of Nrf2/HO-1 (all P < 0.05).
Activation of Nrf2/HO-1 pathway significantly reduced the apoptosis and injury of RGCs in rats with chronic ocular hypertension (COH), thereby protecting RGCs in glaucoma, which could be a promising clinical target to prevent RGC degeneration in glaucoma.
KeywordsGlaucoma Nrf2/HO-1 pathway Retinal ganglion cells Apoptosis
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Pang Y, Wang C, Yu L (2015) Mitochondria-targeted antioxidant ss-31 is a potential novel ophthalmic medication for neuroprotection in glaucoma. Med Hypothesis Discov Innov Ophthalmol 4:120–126Google Scholar
- 2.Sun XB, Lu HE, Chen Y, Fan XH, Tong B (2014) Effect of lithium chloride on endoplasmic reticulum stress-related perk/rock signaling in a rat model of glaucoma. Pharmazie 69:889–893Google Scholar
- 3.Mossböck G, Weger M, Faschinger C, Schmut O, Renner W (2004) Primary open-angle glaucoma. N Engl J Med 363(9422):1711Google Scholar
- 8.McKinnon SJ, Goldberg LD, Peeples P, Walt JG, Bramley TJ (2008) Current management of glaucoma and the need for complete therapy. Am J Manag Care 14:S20–S27Google Scholar
- 20.Bayne K (1996) Revised guide for the care and use of laboratory animals available. Am Phys Soc Physiol 39(199):111–208Google Scholar
- 27.Keum YS, Yu S, Chang PP, Yuan X, Kim JH, Xu C, Han J, Agarwal A, Kong AN (2006) Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein kinase isoforms contributing to the induction of antioxidant response element-mediated heme oxygenase-1 in human hepatoma HepG2 cells. Cancer Res 66:8804–8813CrossRefGoogle Scholar
- 39.Duan P, Hu C, Butler HJ, Quan C, Chen W, Huang W, Tang S, Zhou W, Yuan M, Shi Y, Martin FL, Yang K (2017) 4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/Fasl signaling. Environ Toxicol 32:739–753CrossRefGoogle Scholar
- 41.Huang W, Fileta JB, Dobberfuhl A, Filippopolous T, Guo Y, Kwon G, Grosskreutz CL (2005) Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma. Proc Natl Acad Sci U S A 102:12242–12247CrossRefGoogle Scholar