Work

Oxidative stress promotes the progression of age-related macular degeneration by up-regulating Spp1 to activate the JAK/STAT signaling pathway

Year: 2026

Type: article

Abstract: Age-related macular degeneration (AMD) is the leading cause of visual impairment in elderly people, and due to the unclear specific pathogenesis, eradication treatment cannot be carried out. This study aims to explore the molecular regulatory network and signal transduction mechanism related to the pathogenesis of AMD, with the expectation of providing a theoretical basis for the analysis of the pathological mechanism of AMD and the discovery of potential therapeutic targets. Sodium iodate (NaIO3) was used to induce AMD in mice, and optical coherence tomography (OCT) was used to detect macular degeneration and retinal thickness in their eyes. Differentially expressed mRNAs or proteins were then obtained using differential analysis. Gene set enrichment analysis (GSEA) was used to identify underlying signaling pathways associated with AMD. ARPE-19 cells were induced with H2O2, and cellular oxidative stress was evaluated. Secreted phosphoprotein 1 (SPP1) expression was verified using quantitative real-time PCR (qRT-PCR) and western blot (WB). The relationship between SPP1 expression and signaling pathways was verified using the WB assay. Cell counting kit 8 (CCK-8) was performed to verify the effect of secreted SPP1 expression on the survival of retinal pigment epithelium (RPE) cells. Transcriptomic and proteomic analyses revealed that SPP1 was significantly upregulated in AMD, and a key pathway was obtained: the JAK-STAT signaling pathway. In vitro experiments showed that SPP1 was significantly over-expressed in the AMD group, accompanied by elevated oxidative stress levels. Furthermore, SPP1 knockdown indirectly suppressed JAK-STAT pathway activation by downregulating CD44 expression, thereby contributing to the survival of RPE cells. Overall, this study demonstrates that oxidative stress may promote AMD progression by impairing RPE cell survival through inducing SPP1-mediated CD44 upregulation and JAK-STAT pathway activation.

Source: Scientific Reports

DOI: 10.1038/s41598-026-48556-6

Authors: Qi Zeng, Xingyu Hua, Yutong Liu, Sha Wang

Institutions: Hunan Normal University, Hunan Provincial People's Hospital, Central South University, Xiangya Hospital Central South University

Language: English

Topic: Retinal Diseases and Treatments

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690