Journal Article

Hyperoside protects against oxidative stress-mediated photoreceptor degeneration: therapeutic potentials for photoreceptor degenerative diseases

Wang, Yujue, Xu, Jing, Du, Xiaoye, Cui, Jingang, Wang, Peiwei, Zhang, Teng, Li, Daijin, Chang, Jie, Wu, Hanhan, Chen, Yu

2023

Overview

Background Photoreceptor degeneration underpinned by oxidative stress-mediated mitochondrial dysfunction and cell death leads to progressive and irreversible vision impairment. Drug treatments that protect against photoreceptor degeneration are currently available in the clinical settings. It has been shown that hyperoside, a flavonol glycoside, protects against neuronal loss in part by suppressing oxidative stress and maintaining the functional integrity of mitochondria. However, whether hyperoside protects against photoreceptor degeneration remains unknown. Methods To address the pharmacological potentials of hyperoside against oxidative stress-mediated photoreceptor degeneration on molecular, cellular, structural and functional levels, multiple in vitro and in vivo methodologies were employed in the current study, including live-cell imaging, optical coherence tomography, electroretinography, histological/immunohistochemical examinations, transmission electron microscopy, RNA-sequencing and real-time qPCR. Results The in vitro results demonstrate that hyperoside suppresses oxidative stress-mediated photoreceptor cell death in part by mitigating mitochondrial dysfunction. The in vivo results reveal that hyperoside protects against photooxidative stress-induced photoreceptor morphological, functional and ultrastructural degeneration. Meanwhile, hyperoside treatment offsets the deleterious impact of photooxidative stress on multiple molecular pathways implicated in the pathogenesis of photoreceptor degeneration. Lastly, hyperoside attenuates photoreceptor degeneration-associated microglial inflammatory activation and reactive Müller cell gliosis. Conclusions All things considered, the present study demonstrates for the first time that hyperoside attenuates oxidative stress-induced photoreceptor mitochondrial dysfunction and cell death. The photoreceptor-intrinsic protective effects of hyperoside are corroborated by hyperoside-conferred protection against photooxidative stress-mediated photoreceptor degeneration and perturbation in retinal homeostasis, warranting further evaluation of hyperoside as a photoreceptor protective agent for the treatment of related photoreceptor degenerative diseases.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Alzheimer's disease / Analysis / Apoptosis / Bioflavonoids / Biomedical and Life Sciences / Biomedicine / Care and treatment / Cell activation / Cell death / Degenerative diseases / Diagnosis / Flavones / Flavonoids / Flavonols / Gliosis / Health aspects / Homeostasis / Hyperoside / Inflammation / Ketamine / Laboratory animals / Medicine/Public Health / Mitochondria / Oxidation / Oxidative stress / Penicillin / Permeability / Photoreceptor degeneration / Photoreceptors / Physiological aspects / Retina / Retinal degeneration / Retinal diseases / Retinal homeostasis / Scientific equipment and supplies industry / Structure-function relationships / Traditional Chinese medicine / Translational Ophthalmology / Transmission electron microscopy / Visual impairment