Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b-HSVTK mouse model

Acta Ophthalmol. 2018 Nov;96(7):e789-e796. doi: 10.1111/aos.13716. Epub 2018 Mar 14.

Abstract

Purpose: To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b-HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells.

Methods: We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b-HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14.

Results: The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2 ) and peripheral retina (53 ± 20.6 cells/mm2 ); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2 , p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups.

Conclusion: The CD11b-HSVTK mouse is a feasible model for a local depletion of CD11b+ cells in the retina. Nevertheless, only a partial depletion of CD11b+ cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected.

Keywords: HSVTK; CD11b; intravitreal injection; laser-induced neovascularization; macrophages; microglia.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • CD11b Antigen / physiology*
  • Calcium-Binding Proteins / physiology
  • Cell Count
  • Choroidal Neovascularization / metabolism
  • Choroidal Neovascularization / physiopathology*
  • Disease Models, Animal*
  • Female
  • Ganciclovir / pharmacology
  • Intravitreal Injections
  • Laser Coagulation
  • Macrophages / immunology*
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / physiology
  • Microglia / immunology*
  • Microglia / pathology
  • Polymerase Chain Reaction
  • Simplexvirus / enzymology
  • Thymidine Kinase / genetics

Substances

  • Aif1 protein, mouse
  • Antiviral Agents
  • CD11b Antigen
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Thymidine Kinase
  • Ganciclovir