Abstract
Purpose :
Hypobaric hypoxia has detrimental effects on retinal function, but the detail mechanisms underlying this dysfunction remain unclarified. Optic nerve sheath is an essential part to protect the optic nerve and retinal function. Our current investigation is to explore the impact that hypobaric hypoxia imposes on optic nerve sheath, and evaluate the intervention efficacy of hesperidin (HSD) on the hypobaric hypoxia-induced impairment to the optic nerve sheath.
Methods :
Experiment rats were randomly grouped as the control, hypobaric hypoxia group and HSD intervention group. A low-pressure oxygen cabin was used to mimic 5000m altitude. We utilized TUNEL assay and immunohistochemical technique to determine the apoptotic changes in the optic nerve sheath following different treatments for 7 days. The protein levels of inflammatory cytokines were assessed by Elisa assay. We used qRT-PCR to analyze mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) and the tight junction of the optic nerve sheath.
Results :
We found that hypobaric hypoxia remarkably decreased Nrf2/HO-1levels, elevated TUNEL-positive cells in the optic nerve sheath, induced the reduction of Bcl-2, elevation of caspase3 and caspase9 expression as well as Bax level. HSD ameliorated the hypobaric hypoxia-caused impairment on optic nerve sheath by activating Nrf2/HO-1 pathway, inhibiting apoptotic caspases expression, reducing Bax and enhancing Bcl-2 expression. Hypobaric hypoxia exposure resulted in the reduction of mRNA expression of occludin, claudin, and Zo-1 in the optic nerve sheath. HSD intervention enhanced the mRNA levels of the tight junction genes. Additionally, hypobaric hypoxia triggered inflammatory cytokines release in the optic nerve sheath via increasing protein levels of IL-6, IL-1β, and TNF-α. The administration of HSD inhibited hypobaric hypoxia-initiated inflammatory response through reducing the inflammatory cytokines release.
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Conclusions :
Our findings suggest that hypobaric hypoxia exerts a pathological impact on the rat optic nerve sheath through inhibiting Nrf2/HO-1 pathway, activating mitochondrial apoptotic pathway, triggering inflammatory cytokines release and affecting tight junction of the sheath. The intervention of HSD exhibits a protective role in the hypobaric hypoxia-induced stress on the optic nerve sheath.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.