Neutrophils promote laser-induced choroidal neovascularization by increasing pro-inflammatory cytokines secretion and cell cycle arrest in retinal pigment epithelium.

Autor: Fan Q; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China; Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China; Jinan Clinical Research Center for Geriatric Medicine (202132001), Jinan, Shandong Province, China., Song X; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China., Li M; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China; Jinan Clinical Research Center for Geriatric Medicine (202132001), Jinan, Shandong Province, China., Xu Q; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China., Yan C; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China., Li H; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China., Qu Y; Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China; Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China; Jinan Clinical Research Center for Geriatric Medicine (202132001), Jinan, Shandong Province, China. Electronic address: yiqucn@sdu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2025 Jan 03; Vol. 145, pp. 113735. Date of Electronic Publication: 2024 Dec 06.
DOI: 10.1016/j.intimp.2024.113735
Abstrakt: Inflammation is hypothesized to have essential functions in the development of wet age-related macular degeneration (AMD). Polymorphonuclear neutrophils (PMNs), recognized as major players in inflammation, are typically the first leukocytes to be recruited to an inflammatory site. Previous studies have identified neutrophil aggregates in the lesion site of the choroidal neovascularization model, and systemic depletion of neutrophils in adult mice is associated with reduced choroidal neovascularization (CNV) area, suggesting a pivotal role of PMNs in CNV pathogenesis. Here, we investigate the role of neutrophils in promoting CNV, a key feature of wet AMD. The malfunction and demise of retinal pigment epithelium cells are essential elements in CNV pathogenesis. Our hypothesis posits that neutrophils exacerbate CNV by influencing pro-inflammatory cytokines secreted by retinal pigment epithelium (RPE) cells. Using in vivo laser-induced CNV models with mice and in vitro experiments with the human ARPE-19 cell line, we demonstrated that co-culturing neutrophils with ARPE-19 cells induces an increase in pro-inflammatory cytokines and leads to S-phase cell cycle arrest, potentially through the induction of double-strand breaks (DSBs). Further exploration of this interaction revealed a potential pathway involving reactive oxygen species (ROS) and microRNA-23a, wherein PMNs induce DSBs by initiating the downregulation of LB1 via microRNA-23a. Additionally, we found that dHL-60 cell line could serve as a substitute for primary PMNs, highlighting its potential as a valuable tool in experimental models involving interactions with retinal cells. Our findings underscore the significant role of neutrophils in CNV pathogenesis, providing insights into potential therapeutic targets for wet AMD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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