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


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
StatePublished - 2021

Bibliographical note

Funding Information:
This study was supported in part by grants from the Israel Science Foundation (#1006/13) and the Israeli Ministry of Health (#9184). These funding sources had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The raw data used in this study will be made available upon reasonable request to the corresponding author at (

Publisher Copyright:
© 2021 Molecular Vision.


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