Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
Berlin Institute of Health (BIH), Berlin, Germany.
Acta Ophthalmol. 2018 Nov;96(7):e789-e796. doi: 10.1111/aos.13716. Epub 2018 Mar 14.
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.
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 ) and peripheral retina (53 ± 20.6 cells/mm ); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm , p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups.
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.
评估视网膜巨噬细胞和小胶质细胞对脉络膜新生血管（CNV）形成的影响。因此，我们使用了一种转基因小鼠（CD11b-HSVTK），其中应用更昔洛韦（GCV）可导致 CD11b 细胞耗竭。
我们首先研究了在视网膜中局部耗尽 CD11b 巨噬细胞和小胶质细胞是否可行。在第二步中，分析了 CD11b 细胞耗竭对 CNV 形成的影响。每只 CD11b-HSVTK 小鼠的一只眼注射 GCV，另一只眼注射生理盐水（NaCl）。在第 3 天和第 7 天（单次注射）或第 14 天和第 21 天（两次注射）进行细胞计数。通过氩激光诱导脉络膜新生血管（CNV），并在第 14 天进行分析。
单次注射后 7 天和两次注射 GCV 后 14 天，可达到最有效的 CD11b 细胞耗竭。两次注射 GCV 后，我们发现中央（52±23.9 个细胞/mm）和周边视网膜（53±20.6 个细胞/mm）中的 CD11b 细胞明显减少；与接受 NaCl 的眼睛相比（分别为 216±49.0 和 210±50.5 个细胞/mm，p<0.001）。关于 CNV 面积，各组之间无统计学意义。
CD11b-HSVTK 小鼠是一种可行的模型，可用于在视网膜中局部耗尽 CD11b 细胞。然而，与没有任何眼内注射的基线数据相比，只能实现 CD11b 细胞的部分耗竭。我们的结果并未显示 CNV 面积的显著减少。根据以往的知识，系统免疫细胞对 CNV 形成的潜在影响可能比预期的更为重要。
