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

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 macrophages 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.

SUBMITTER: Hagbi-Levi S

PROVIDER: S-EPMC8645186 | biostudies-literature |

REPOSITORIES: biostudies-literature

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