Anti-tumor necrosis factor alpha reduces the proangiogenic effectof activated macrophages derived from patients with age-related macular degeneration

Shira Hagbi-Levi, Liran Tiosano, Batya Rinsky, Nadav Levinger, Sarah Elbaz-Hayoun, Shai Carmi, Michelle Grunin, Itay Chowers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Purpose: Macrophages are believed to promote choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nvAMD); however, the underlying proangiogenic mechanism is poorly understood. Therefore, we examined this mechanism in proinflammatory macrophages derived from patients with nvAMD. Methods: Monocytes were isolated from patients with nvAMD and polarized to form an M1 proangiogenic phenotype. We then screened for the role of proangiogenic cytokines expressed by these macrophages, including TNF-α, VEGF, IL-6, IL-8, and IL-1β, using an ex vivo choroid sprouting assay and an in vivo rodent model of laser-induced CNV (LI-CNV). We also examined the value of inhibiting TNF-α inhibition with respect to reducing the proangiogenic effects of M1 macrophages. Finally, we analyzed the macrophage cytokine expression database to evaluate the feasibility of modulating the expression of TNF-α. Results: The cytokines above are expressed at high levels in patient-derived M1 macrophages. However, among the cytokines tested only TNF-α significantly increased choroid sprouting. Moreover, adoptive intravitreal transfer of M1 macrophages significantly increased LI-CNV, and blocking TNF-α abolished the proangiogenic effects of M1 macro-phages in both models. An analysis of cytokine expression revealed that >50% of TNF-α expression is determined by modifiable factors. Conclusions: Blocking TNF-α can reduce the proangiogenic effects of M1 macrophages in nvAMD. Thus, activated macrophages may represent a potential therapeutic target for altering TNF-α expression in nvAMD.

Original languageAmerican English
Pages (from-to)622-631
Number of pages10
JournalMolecular Vision
Volume27
StatePublished - 2021

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© 2021 Molecular Vision.

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