bims-mideyd 2025-01-26 papers

Int J Ophthalmol. 2025 ;18(1): 28-38

Autophagy serves as a protective effect against inflammatory injury of oxidative stress in ARPE-19 cell.

Na-Na Meng, Lei-Zhou Xia, Yi-Qing Gong, Pei-Rong Lu.

AIM: To test the effect of autophagy on inflammatory damage resulting from oxidative stress in adult retinal pigment epithelial cell line (ARPE-19).
METHODS: ARPE-19 cells were pretreated with 200 and 600 µmol/L hydrogen peroxide (H2O2) at various time intervals. The changes of cell morphology, cell viability, reactive oxygen species (ROS) level, autophagic activity, and the inflammatory cytokines (TNFα, IL-6, and TGFβ) were measured at baseline and after treatment with autophagy inducer rapamycin (Rapa) and suppressor wortmannin (Wort) or shATG5.
RESULTS: The levels of ROS, cytokines (TNFα, IL-6, and TGFβ), and autophagic activity were significantly increased in ARPE-19 cells after pretreated with H2O2 (all P<0.05) and IL-10 was significantly decreased (P<0.05). By upregulating autophagy, Rapa significantly reduced oxidative stress-induced secretion of pro-inflammatory factors (TNFα and IL-6) and ROS (all P<0.05), yet elevated the production of TGFβ (P<0.05). In contrast, suppression of autophagy through Wort or ATG5 knockdown reduced cell viability, increased cell apoptotic rate, and exacerbated the generation of ROS and inflammatory cytokines (TNFα, IL-6, and TGFβ; all P<0.05).
CONCLUSION: Autophagy demonstrates a protective effect on ARPE-19 cell through mitigating oxidative damage and oxidative stress-induced inflammatory response. Regulation of autophagy may be a potential way for age-related macular degeneration.

Keywords: autophagy; inflammation; reactive oxygen species; retinal pigment epithelium

DOI: https://doi.org/10.18240/ijo.2025.01.04

Phytomedicine. 2025 Jan 18. pii: S0944-7113(25)00047-9. [Epub ahead of print]138 156408

Astragaloside IV inhibits retinal pigment epithelial cell senescence and reduces IL-1β mRNA stability by targeting FTO-mediated m6A methylation.

Si-Wei Wang, Ping Li, Shi-Yu Liu, De-Lian Huang, Si-Jia Zhang, Xi-Xi Zeng, Tian Lan, Kai-Li Mao, Yuan Gao, Yi-Fan Cheng, Qing Shen, Ye-Ping Ruan, Zhu-Jun Mao.

BACKGROUND: Resistance to senescence in retinal pigment epithelial (RPE) cells can delay the progression of age-related macular degeneration (AMD). However, the mechanisms underlying RPE cell senescence remain inadequately understood, and effective therapeutic strategies are lacking. While astragaloside IV (Ast) has demonstrated anti-aging properties, its specific effects on RPE cell senescence and potential mechanisms are not yet fully clarified.
PURPOSE: This study aimed to explore the impacts of Ast on RPE cell senescence and to uncover the molecular mechanisms involved.
METHODS: The therapeutic efficacy of Ast was assessed using sodium iodate (NaIO3)-induced adult retinal pigment epithelial cell line 19 (ARPE-19) cell models and an AMD mouse model. To investigate the mechanisms by which Ast mitigated RPE cell senescence, RNA sequencing (RNA-seq), drug affinity responsive target stability-mass spectrometry (DARTS-MS), cellular thermal shift assay (CETSA), reverse transcription quantitative PCR (RT-qPCR), as well as western blotting were conducted.
RESULTS: Ast significantly inhibited NaIO3-treated ARPE-19 cell senescence and protected against NaIO3-induced AMD in mice. RNA-seq analysis revealed that Ast significantly attenuated inflammation-related signaling pathways and reduced the mRNA levels of interleukin-1 beta (IL-1β). Specifically, Ast decreased the stability of IL-1β mRNA while enhancing its N6-methyladenosine (m6A) methylation. Furthermore, Ast directly interacted with fat mass and obesity-associated protein (FTO). Knockdown or pharmacological inhibition of FTO mitigated the senescence and IL-1β expression in NaIO3-treated ARPE-19 cells. FTO was essential for Ast to inhibit cellular senescence and IL-1β expression. Additionally, inhibition or knockdown of FTO conferred also provided resistance to AMD in the murine model.
CONCLUSION: Our results indicated that Ast significantly attenuated RPE cell senescence and showed anti-AMD properties. FTO was demonstrated to be a promising therapeutic target for AMD treatment. These findings may provide a deeper understanding of the molecular mechanisms underlying RPE cell senescence in AMD and offer potential strategies for its prevention and management.

Keywords: Astragaloside IV; Cell senescence; FTO; IL-1β; Retinal pigment epithelial cell; m(6)A methylation

DOI: https://doi.org/10.1016/j.phymed.2025.156408

Int J Ophthalmol. 2025 ;18(1): 15-27

IL-17A mediates inflammation-related retinal pigment epithelial cells injury via ERK signaling pathway.

Hui-Min Zhong, Bing-Qiao Shen, Yu-Hong Chen, Xiao-Huan Zhao, Xiao-Xu Huang, Min-Wen Zhou, Xiao-Dong Sun.

AIM: To investigate whether interleukin-17A (IL-17A) gets involved in the mechanisms of inflammation-related retinal pigment epithelium (RPE) cells injury and its significance in age-related macular degeneration (AMD).
MRTHODS: A sodium iodate (NaIO3) mouse model as well as IL-17A -/- mice were established. The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro, were investigated using immunofluorescence, immunoprotein blotting, and quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), respectively. Interventions using recombinant IL-17A protein (rIL-17A) or IL-17A neutralizing antibody (IL-17A NAb) were used to observe the subsequent differences in fundus, fundus photography and optical coherence tomography (OCT), cell viability, and expression of oxidative stress-related markers before and after modeling, and to screen for key signaling pathways.
RESULTS: In the scenario of NaIO3 stimulation, RPE cells obviously tended to degenerate. Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice, whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A -/- mice. In addition, IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo. Meanwhile, the extracellular signal-regulated kinase (ERK) signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo, as IL-17A-induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.
CONCLUSION: IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway. Inhibition of IL-17A may be a new potential target for dry AMD treatment.

Keywords: IL-17A; NaIO3; age-related macular degeneration; microglia; retinal pigment epithelium

DOI: https://doi.org/10.18240/ijo.2025.01.03

Int J Ophthalmol. 2025 ;18(1): 160-167

Glaucomatous retinal ganglion cells: death and protection.

Na Cui, Jun Jia, Yuan He.

Glaucoma is a group of diseases characterized by progressive optic nerve degeneration, with the characteristic pathological change being death of retinal ganglion cells (RGCs), which ultimately causes visual field loss and irreversible blindness. Elevated intraocular pressure (IOP) remains the most important risk factor for glaucoma, but the exact mechanism responsible for the death of RGCs is currently unknown. Neurotrophic factor deficiency, impaired mitochondrial structure and function, disrupted axonal transport, disturbed Ca2+ homeostasis, and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma. This review was conducted using Web of Science, PubMed, Project, and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma, in addition to outlining protective treatments to improve the degradation of RGCs.

Keywords: axonal deletion; glaucoma; neuroprotection; progressive death; retinal ganglion cells

DOI: https://doi.org/10.18240/ijo.2025.01.20