Activation of Nrf2/HO-1 pathway protects retinal ganglion cells from a rat chronic ocular hypertension model of glaucoma.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.