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other·ophthalmology, retina, immunology, preclinical research, biomedical research·PMC10659061

Vascular Cell Adhesion Molecule-1 (VCAM-1) contributes to macular fibrosis in neovascular age-related macular degeneration through modulating macrophage functions

Immunity & Ageing : I & A · 13 authors, 4 centres

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TL;DR

This study found that aqueous humor levels of VCAM-1 were significantly higher in nAMD patients with macular fibrosis compared to those without. In a mouse model, blocking VCAM-1 reduced macrophage infiltration and subretinal fibrosis.

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The study investigated the role of adhesion molecules in macular fibrosis associated with neovascular age-related macular degeneration (nAMD). It measured intraocular levels of several adhesion molecules in nAMD patients and age-matched cataract controls, finding that VCAM-1 levels were specifically elevated in patients with macular fibrosis. In vitro, VCAM-1 promoted macrophage migration and altered gene expression towards a profibrotic phenotype. The findings suggest VCAM-1 as a potential therapeutic target for preventing macular fibrosis in nAMD.

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other

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ophthalmology

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100% · A

ORIGINAL PAPER

PMC10659061

Vascular Cell Adhesion Molecule-1 (VCAM-1) contributes to macular fibrosis in neovascular age-related macular degeneration through modulating macrophage functions

Immunity & Ageing : I & A

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ABSTRACT

Background Neovascular age-related macular degeneration (nAMD) is a major cause of blindness in the elderly. The disease is due to the growth of abnormal blood vessels into the macula, leading to the loss of central vision. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors (e.g., anti-VEGF) is the standard of care for nAMD. However, nearly 50% of patients do not respond or respond poorly to the therapy. More importantly, up to 70% of nAMD patients develop macular fibrosis after 10 years of anti-VEGF therapy. The underlying mechanism of nAMD-mediated macular fibrosis is unknown although inflammation is known to play an important role in the development of abnormal macular blood vessels and its progression to fibro-vascular membrane. In this study, we measured the intraocular levels of adhesion molecule VCAM-1, ICAM-1, CD44, CD62L, and CD62P in nAMD patients with and without macular fibrosis and investigated the link between the levels of adhesion molecule and clinical features (e.g., visual improvement, retinal thickness, etc.). We further investigated the effect of VCAM-1 in macrophage function in vitro and the development of subretinal fibrosis in vivo using a two-stage laser-induced protocol. Results The aqueous levels of ICAM-1, VCAM-1, CD44, and CD62L were significantly higher in nAMD patients compared to cataract controls. The aqueous level of VCAM-1 (but not other adhesion molecules) was significantly higher in patients with macular fibrosis than those without and the level correlated positively with the retinal thickness. VCAM-1 was highly expressed at the lesion site in the mouse model of subretinal fibrosis. Blocking VCAM-1 or its receptor VLA-4 significantly prevented macrophage infiltration and reduced subretinal fibrosis in vivo. VCAM-1 induced macrophage migration and upregulated the expression of Arg-1, Mmp12 and Il6 but down-regulated the expression of iNOS and Il1b in macrophages. Conclusions VCAM-1 may contribute to the development of macular fibrosis in nAMD patients by modulating macrophage functions, including migration and profibrotic polarization. Supplementary Information The online version contains supplementary material available at 10.1186/s12979-023-00389-x.

CITATION EXPORT

Wen Deng, Caijiao Yi, Wei Pan et al.. Vascular Cell Adhesion Molecule-1 (VCAM-1) contributes to macular fibrosis in neovascular age-related macular degeneration through modulating macrophage functions. Immunity & Ageing : I & A. (2023). https://doi.org/10.1186/s12979-023-00389-x

AUTHORS

13 · 4 CENTRES

Wen Deng, Caijiao Yi, Wei Pan, Jian Liu, Jinyan Qi, Juan Chen, Zengchao Zhou, Yiqin Duan, Xiangyan Ning, Jun Li, Changhua Ye, Zhongping Chen, Heping Xu

1https://ror.org/00f1zfq44grid.216417.70000 0001 0379 7164Aier School of Ophthalmology, Central South University, Changsha, China
2Aier Institute of Optometry and Vision Science, Changsha, China
3Changsha Aier Eye Hospital, Changsha, China
4https://ror.org/00hswnk62grid.4777.30000 0004 0374 7521Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, BT9 7BL UK