Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)

Adrian Will-Orrego1, Yubin Qiu1, Elizabeth S Fassbender1

  • 1Department of Ophthalmology, Novartis Institutes for Biomedical Research , Cambridge, Massachusetts.

Abstract

Insights

Mononuclear phagocytes (MNPs) infiltrate choroidal neovascularization (CNV) lesions. Therapies targeting CNV angiogenesis did not alter MNP infiltration, suggesting MNP number is independent of lesion size.

Area of Science:

  • Ophthalmology
  • Immunology
  • Angiogenesis research

Background:

  • Mononuclear phagocytes (MNPs) are key players in neovascular age-related macular degeneration (nv AMD), also known as choroidal neovascularization (CNV).
  • The density and characteristics of MNPs within CNV lesions are influenced by the local microenvironment and therapeutic interventions.
  • Understanding MNP behavior is crucial for developing effective treatments for AMD.

Purpose of the Study:

  • To investigate ocular cell infiltration, specifically MNPs, in a laser-induced mouse model of CNV.
  • To explore conditions that modulate angiogenesis and MNP infiltration in the context of CNV.
  • To assess the impact of toll-like receptor-2 (TLR-2) activation, anti-VEGF therapy, and Ccl2 deletion on MNP dynamics.

Main Methods:

  • Developed and utilized specific assays to quantify MNP numbers in subretinal spaces and within CNV lesions in a mouse model.
  • Administered a TLR-2 activating peptide to assess its effect on CNV and MNP infiltration.
  • Utilized anti-VEGF therapy and Ccl2 genetic deletion to evaluate their influence on angiogenesis and MNP infiltration.

Main Results:

  • Laser injury successfully induced CNV and subsequent MNP infiltration.
  • TLR-2 activation significantly increased CNV area, MNP numbers, and MNP density.
  • Anti-VEGF therapy reduced CNV area, while Ccl2 deletion increased it; however, MNP infiltration remained unchanged in both cases.
  • Surprisingly, MNP infiltration levels did not correlate with the extent of CNV angiogenesis under anti-VEGF or Ccl2-deleted conditions.

Conclusions:

  • Quantification of MNPs offers valuable biological insights for potential AMD therapies.
  • The number of infiltrating MNPs does not appear to directly correlate with the size of laser-induced CNV lesions.
  • These findings suggest that MNP infiltration may be regulated independently of the degree of angiogenesis in CNV.

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