Nobiletin protects retinal ganglion cells in models of ocular hypertension in vivo and hypoxia in vitro.

Feb 13, 2023

Experts: Dan-Dan Wang,Feng-Juan Gao,Xue-Jin Zhang,Fang-Yuan Hu,Ping Xu,Ji-Hong Wu

Glaucoma, a common cause of blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs). Growing evidence suggests that nobiletin (NOB) is a promising neuroprotective drug; however, its effects on glaucomatous neurodegeneration remain unknown. Using rat models of microbead occlusion in vivo and primary RGCs model of hypoxia in vitro, we first demonstrate that NOB reduces RGC apoptosis by a TUNEL assay, Hoechst 33342 staining and FluoroGold (FG) retrograde labeling. This effect does not depend on intraocular pressure (IOP) lowering. Additionally, NOB partially restored the functional and structural damage of inner retinas, attenuated Müller glial activation and oxidative stress caused by ocular hypertension. At 2 weeks after IOP elevation, NOB further enhanced Nrf2/HO-1 pathway in RGCs to withstand the cumulative damage of ocular hypertension. With the administration of HO-1 inhibitor tin-protoporphyrin IX (SnPP), the protective effect of NOB was attenuated. Overall, these results indicate that NOB exerts an outstanding neuroprotective effect on RGCs of glaucomatous neurodegeneration. Besides, interventions to enhance activation of Nrf2/HO-1 pathway can slow the loss of RGCs and are viable therapies for glaucoma.
Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.

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ABOUT THE EXPERTS

Dan-Dan Wang,Feng-Juan Gao,Xue-Jin Zhang,Fang-Yuan Hu,Ping Xu,Ji-Hong Wu

Dan-Dan Wang

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.

Feng-Juan Gao

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.

Xue-Jin Zhang

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.

Fang-Yuan Hu

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.

Ping Xu

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.

Ji-Hong Wu

Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China. Electronic address: jihongwu@fudan.edu.cn.