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

被引:6
作者
Brockmann, Claudia [1 ,2 ]
Kociok, Norbert [1 ,2 ]
Dege, Sabrina [1 ,2 ]
Davids, Anja-Maria [1 ,2 ]
Brockmann, Tobias [1 ,2 ]
Miller, Kelly R. [2 ,3 ]
Joussen, Antonia M. [1 ,2 ]
机构
[1] Humboldt Univ, Freie Univ Berlin, Charite Univ Med Berlin, Dept Ophthalmol, Berlin, Germany
[2] Berlin Inst Hlth, Berlin, Germany
[3] Humboldt Univ, Freie Univ Berlin, Charite Univ Med Berlin, Dept Neuropathol, Berlin, Germany
关键词
CD11b; HSVTK; intravitreal injection; laser-induced neovascularization; macrophages; microglia; MACULAR DEGENERATION; THYMIDINE KINASE; MICROGLIA; ACTIVATION; RETINA; RANIBIZUMAB; GANCICLOVIR; AFLIBERCEPT; MAINTENANCE; MACROPHAGES;
D O I
10.1111/aos.13716
中图分类号
R77 [眼科学];
学科分类号
100212 [眼科学];
摘要
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 Results 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. 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/mm(2)) and peripheral retina (53 +/- 20.6 cells/mm(2)); compared to eyes received NaCl (216 +/- 49.0 and 210 +/- 50.5 cells/mm(2), 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.
引用
收藏
页码:E789 / E796
页数:8
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