Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (2): 378-393.doi: 10.4103/NRR.NRR-D-23-01642

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Subretinal fibrosis secondary to neovascular age-related macular degeneration: mechanisms and potential therapeutic targets

Jingxiang Zhang1, #, Xia Sheng1, #, Quanju Ding1, #, Yujun Wang2, *, Jiwei Zhao1, *, Jingfa Zhang3, 4, *   

  1. 1 Department of Ophthalmology, People’s Hospital of Huangdao District, Qingdao, Shandong Province, China; 2 Department of Urology, People’s Hospital of Huangdao District, Qingdao, Shandong Province, China; 3 Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; 4 National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
  • Online:2025-02-15 Published:2024-06-18
  • Contact: Yujun Wang, MSc, wyj1979wyj@sina.com; Jiwei Zhao, BS, jiaonanzhaojiwei@163.com; Jingfa Zhang, MD, PhD, 13917311571@139.com.
  • Supported by:
    This work was supported by grants from National Key R&D Program of China, No. 2023YFC2506100 (to JZ) and the National Natural Science Foundation of China, No. 82171062 (to JZ).

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Abstract: Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration. It causes local damage to photoreceptors, retinal pigment epithelium, and choroidal vessels, which leads to permanent central vision loss of patients with neovascular age-related macular degeneration. The pathogenesis of subretinal fibrosis is complex, and the underlying mechanisms are largely unknown. Therefore, there are no effective treatment options. A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments. The current article reviews several aspects of subretinal fibrosis, including the current understanding on the relationship between neovascular agerelated macular degeneration and subretinal fibrosis; multimodal imaging techniques for subretinal fibrosis; animal models for studying subretinal fibrosis; cellular and non-cellular constituents of subretinal fibrosis; pathophysiological mechanisms involved in subretinal fibrosis, such as aging, infiltration of macrophages, different sources of mesenchymal transition to myofibroblast, and activation of complement system and immune cells; and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis, such as vascular endothelial growth factor, connective tissue growth factor, fibroblast growth factor 2, platelet-derived growth factor and platelet-derived growth factor receptor-β, transforming growth factor-β signaling pathway, Wnt signaling pathway, and the axis of heat shock protein 70–Toll-like receptors 2/4–interleukin-10. This review will improve the understanding of the pathogenesis of subretinal fibrosis, allow the discovery of molecular targets, and explore potential treatments for the management of subretinal fibrosis.

Key words: choroidal neovascularization, epithelial-mesenchymal transition, mesenchymal transition, myofibroblast, neovascular age-related macular degeneration, submacular fibrosis, subretinal fibrosis, therapeutic targets, transforming growth factor-β, vascular endothelial growth factor