Abstract

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute vision loss in older people, and there is no effective therapy. The effect of the systemic or local application of steroids for NAION patients remains controversial. Oroxylin A (OA) (5,7-dihydroxy-6-methoxyflavone) is a bioactive flavonoid extracted from Scutellariae baicalensis Georgi. with various beneficial effects, including anti-inflammatory and neuroprotective effects. A previous study showed that OA promotes retinal ganglion cell (RGC) survival after optic nerve (ON) crush injury. The purpose of this research was to further explore the potential actions of OA in ischemic injury in an experimental anterior ischemic optic neuropathy (rAION) rat model induced by photothrombosis. Our results show that OA efficiently attenuated ischemic injury in rats by reducing optic disc edema, the apoptotic death of retinal ganglion cells, and the infiltration of inflammatory cells. Moreover, OA significantly ameliorated the pathologic changes of demyelination, modulated microglial polarization, and preserved visual function after rAION induction. OA activated nuclear factor E2 related factor (Nrf2) signaling and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1 (HO-1) in the retina. We demonstrated that OA activates Nrf2 signaling, protecting retinal ganglion cells from ischemic injury, in the rAION model and could potentially be used as a therapeutic approach in ischemic optic neuropathy.

Highlights

  • Nonarteritic anterior ischemic optic neuropathy (NAION) is one of the most common acute optic neuropathies in the elderly population [1], and it leads to a severe loss of visual function

  • We evaluated the effects of Oroxylin A (OA) on retinal ganglion cell (RGC) survival, th polarization induced by experimental anterior ischemic optic neuropathy remains to be integrity of visual function, neuroinflammation, and microglial polarization in an exper elucidated

  • The fluoro-gold (FG) retrograde labeling of RGCs was performed to determine the neuroprotective effect of OA on the RGCs after infarction

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Summary

Introduction

Nonarteritic anterior ischemic optic neuropathy (NAION) is one of the most common acute optic neuropathies in the elderly population [1], and it leads to a severe loss of visual function. Accumulating evidence suggests that NAION results from impaired vascular autoregulation at the optic nerve head and leads to impaired ocular homeostasis [9,10,11]. These factors contribute to axonal edema and compartment syndrome for the optic nerve disc, further accelerating hypoxia, increasing oxidative stress, and inducing inflammatory processes and the consequential loss of retinal ganglion cells (RGCs) [12,13,14,15,16,17]

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