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

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.