Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models

Jinfeng Liu; Lina Zhou; Xueping Wu; Zihang Chen; Xiaofei Zheng; Huajun Wang; Kwok Fai So; Lan Ma; Jiantao Wang; Kin Chiu

doi:10.3389/fphar.2024.1404119

Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models

Front Pharmacol. 2024 Jul 3:15:1404119. doi: 10.3389/fphar.2024.1404119. eCollection 2024.

Authors

Jinfeng Liu^#^{1

2}, Lina Zhou^#³, Xueping Wu^#⁴, Zihang Chen⁵, Xiaofei Zheng⁵, Huajun Wang⁵, Kwok Fai So^{2

6

7

8}, Lan Ma^#^{9

10

11}, Jiantao Wang^#¹, Kin Chiu^#^{2

6

7}

Affiliations

¹ Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, Shenzhen, China.
² Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
³ Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China.
⁴ Jinzhou Medical University, Jinzhou, China.
⁵ Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, Guangzhou, China.
⁶ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
⁷ Department of Psychology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
⁸ Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
⁹ Institute of Biopharmaceutical and Health Engineering, Tsinghua University Shenzhen Graduate School, Tsinghua University, Shenzhen, China.
¹⁰ Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, China.
¹¹ State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.

^# Contributed equally.

Abstract

Lycium ruthenicum Murray (LR), known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H₂O₂-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

Keywords: Lycium ruthenicum murray; glaucoma; microglia; oxidative stress; retinal ganglion cell.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This project was supported by Midstream Research Program for Universities (MRP, Project No: MRP-092-17X) in Hong Kong to KC.