Molecular pathogenesis of subretinal fibrosis in neovascular AMD focusing on epithelial-mesenchymal transformation of retinal pigment epithelium

Dandan Liu; Chaoyang Zhang; Jingting Zhang; Guo-Tong Xu; Jingfa Zhang

doi:10.1016/j.nbd.2023.106250

Molecular pathogenesis of subretinal fibrosis in neovascular AMD focusing on epithelial-mesenchymal transformation of retinal pigment epithelium

Neurobiol Dis. 2023 Sep:185:106250. doi: 10.1016/j.nbd.2023.106250. Epub 2023 Aug 2.

Authors

Dandan Liu¹, Chaoyang Zhang², Jingting Zhang², Guo-Tong Xu³, Jingfa Zhang⁴

Affiliations

¹ Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
² Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, Shanghai, China; 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.
³ Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China. Electronic address: gtxu@tongji.edu.cn.
⁴ Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, Shanghai, China; 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. Electronic address: 13917311571@139.com.

PMID: 37536385
DOI: 10.1016/j.nbd.2023.106250

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss among elderly people in developed countries. Neovascular AMD (nAMD) accounts for more than 90% of AMD-related vision loss. At present, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is widely used as the first-line therapy to decrease the choroidal and retinal neovascularizations, and thus to improve or maintain the visual acuity of the patients with nAMD. However, about 1/3 patients still progress to irreversible visual impairment due to subretinal fibrosis even with adequate anti-VEGF treatment. Extensive literatures support the critical role of epithelial-mesenchymal transformation (EMT) of retinal pigment epithelium (RPE) in the pathogenesis of subretinal fibrosis in nAMD, but the underlying mechanisms still remain largely unknown. This review summarized the molecular pathogenesis of subretinal fibrosis in nAMD, especially focusing on the transforming growth factor-β (TGF-β)-induced EMT pathways. It was also discussed how these pathways crosstalk and respond to signals from the microenvironment to mediate EMT and contribute to the progression of nAMD-related subretinal fibrosis. Targeting EMT signaling pathways might provide a promising and effective therapeutic strategy to treat subretinal fibrosis secondary to nAMD.

Keywords: EMT; Hedgehog signaling; Neovascular AMD; Subretinal fibrosis; TGF-β signaling; Wnt signaling.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Angiogenesis Inhibitors / metabolism
Angiogenesis Inhibitors / therapeutic use
Epithelial-Mesenchymal Transition
Fibrosis
Humans
Retinal Pigment Epithelium* / metabolism
Retinal Pigment Epithelium* / pathology
Vascular Endothelial Growth Factor A / metabolism
Visual Acuity
Wet Macular Degeneration* / drug therapy
Wet Macular Degeneration* / metabolism
Wet Macular Degeneration* / pathology

Substances

Angiogenesis Inhibitors
Vascular Endothelial Growth Factor A