Quercetin Declines Apoptosis, Ameliorates Mitochondrial Function and Improves Retinal Ganglion Cell Survival and Function in In Vivo Model of Glaucoma in Rat and Retinal Ganglion Cell Culture In Vitro

Abstract

Glaucoma is a progressive neuropathy characterized by the loss of retinal ganglion cells (RGCs). Strategies that delay or halt RGC loss have been recognized as potentially beneficial for rescuing vision in glaucoma patients. Quercetin (Qcn) is a natural and important dietary flavonoid compound, widely distributed in fruits and vegetables. Mounting evidence suggests that Qcn has numerous neuroprotective effects. However, whether Qcn exerts neuroprotective effects on RGC in glaucoma is poorly understood. In this study, we investigated the protective effect of Qcn against RGC damage in a rat chronic ocular hypertension (COHT) model in vivo and hypoxia-induced primary cultured RGC damage in vitro, and we further explored the underlying neuroprotective mechanisms. We found that Qcn not only improved RGC survival and function from a very early stage of COHT in vivo, it promoted the survival of hypoxia-treated primary cultured RGCs in vitro via ameliorating mitochondrial function and preventing mitochondria-mediated apoptosis. Our findings suggest that Qcn has direct protective effects on RGCs that are independent of lowering the intraocular pressure (IOP). Qcn may be a promising therapeutic agent for improving RGC survival and function in glaucomatous neurodegeneration.

Overexpression of Optic Atrophy Type 1 Protects Retinal Ganglion Cells and Upregulates Parkin Expression in Experimental Glaucoma

“…Four days before the first laser treatment, 2 μl of 5% of FluoroGold (FluoroGold; Sigma-Aldrich, St. Louis, MO, United States) was microinjected into the superior colliculus on each side of anesthetized rats, as described previously ( Gao et al, 2017 ). Eyes obtained from the rats 2 weeks after IOP elevation were fixed in 4% paraformaldehyde in PBS and prepared as flat-mount.…”

Protective effects of quercetin in a rodent model of anterior ischemic optic neuropathy (rAION)

“…In the retina, we found that Qcn protected ARPE-19 cells from oxidative stress injury [14]. Other studies reported that Qcn has protective effects in the retina ischemia-reperfusion injury [15], ocular inflammation [16], and neuroprotective effects on RGC in glaucoma [17]. However, whether Qcn protects the RGCs in rAION is poorly understood.…”

“…Furthermore, Qcn preserved the visual function, prevented apoptosis of RGC, decreased the macrophage/microglial infiltration in the ONs, and impeded the secondary RGC death. Qcn was administered by intraperitoneal, oral, or intravitreal injection on the retina as described previously [17,22,23]. However, based on the pharmacodynamic maintenance and prolonged exposure of Qcn on the retina, we selected the intravitreal injection as the mode of Qcn administration.…”

“…However, based on the pharmacodynamic maintenance and prolonged exposure of Qcn on the retina, we selected the intravitreal injection as the mode of Qcn administration. A previous study [17] described the neuroprotective role of Qcn on RGC in a rat chronic ocular hypertension (COHT) model as a reference for the determination of the dose and frequency of Qcn administration.…”

Chemical and molecular characterization of metabolites from Flavobacterium sp.

“…It can be used as a protective agent against coronary diseases [ 38 ]. It has been shown that quercetin is a promising therapeutic agent for improving retinal ganglion cells (RGC) survival and function in glaucomatous neurodegeneration [ 39 ]. Low concentration of quercetin antagonizes glioblastoma cell invasion and angiogenesis in vitro [ 40 ].…”