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A Mouse Model for Laser-induced Choroidal Neovascularization
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Long-term low-dose aspirin promotes laser-induced choroidal neovascularization through suppressing TSP-1 expression.

Caijiao Yi1, Chang Luo1, Jiawu Zhao2

  • 1AIER Eye Institute, Changsha Aier Eye Hospital, Changsha, Hunan, China.

Frontiers in Cellular Neuroscience
|December 22, 2025
PubMed
Summary

Long-term, low-dose aspirin use worsened neovascular age-related macular degeneration (nAMD) in mice by reducing thrombospondin-1 (TSP-1). Lower TSP-1 levels may indicate nAMD risk, warranting further study on aspirin

Keywords:
age-related macular degenerationangiogenesisaspirininflammationmacrophages

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Area of Science:

  • Ophthalmology
  • Immunology
  • Pharmacology

Background:

  • Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss.
  • The role of aspirin in nAMD pathogenesis is not fully understood.
  • Thrombospondin-1 (TSP-1) is implicated in angiogenesis and may be relevant to nAMD.

Purpose of the Study:

  • To investigate the impact of chronic low-dose aspirin on experimental nAMD.
  • To explore the effects of aspirin on immune cells and TSP-1 in the context of nAMD.
  • To assess the relationship between TSP-1 levels and nAMD in patients.

Main Methods:

  • Laser-induced choroidal neovascularization (CNV) model in C57BL/6J and Thbs-1-/- mice treated with aspirin.
  • In vitro studies on bone marrow-derived macrophages (BMDMs) and retinal pigment epithelial (RPE) cells exposed to aspirin.
  • Analysis of immune cell profiles, cytokine gene expression (qRT-PCR), and TSP-1 levels (ELISA).

Main Results:

  • Aspirin increased CNV severity and CD11b+ cells in laser-treated mice, while reducing serum TSP-1.
  • In vitro, aspirin modulated inflammatory gene expression and TSP-1 in M1 BMDMs but not RPE cells.
  • Thbs-1-/- mice exhibited severe CNV unaffected by aspirin; nAMD patients showed lower TSP-1 than controls.

Conclusions:

  • Long-term low-dose aspirin use exacerbates experimental CNV by downregulating TSP-1.
  • Reduced serum TSP-1 may be a risk factor for developing nAMD.
  • Further validation of aspirin's long-term ocular safety in nAMD is needed through prospective studies.