• Media type: E-Article
  • Title: Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b‐HSVTK mouse model
  • Contributor: Brockmann, Claudia; Kociok, Norbert; Dege, Sabrina; Davids, Anja‐Maria; Brockmann, Tobias; Miller, Kelly R.; Joussen, Antonia M.
  • imprint: Wiley, 2018
  • Published in: Acta Ophthalmologica
  • Language: English
  • DOI: 10.1111/aos.13716
  • ISSN: 1755-375X; 1755-3768
  • Keywords: Ophthalmology ; General Medicine
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose</jats:title><jats:p>To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (<jats:styled-content style="fixed-case">CNV</jats:styled-content>). Therefore, we used a transgenic mouse (<jats:styled-content style="fixed-case">CD</jats:styled-content>11b‐<jats:styled-content style="fixed-case">HSVTK</jats:styled-content>) in which the application of ganciclovir (<jats:styled-content style="fixed-case">GCV</jats:styled-content>) results in a depletion of <jats:styled-content style="fixed-case">CD</jats:styled-content>11b<jats:sup>+</jats:sup> cells.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We first investigated if a local depletion of <jats:styled-content style="fixed-case">CD</jats:styled-content>11b<jats:sup>+</jats:sup> macrophages and microglia in the retina is feasible. In a second step, the influence of <jats:styled-content style="fixed-case">CD</jats:styled-content>11b<jats:sup>+</jats:sup> cell depletion on <jats:styled-content style="fixed-case">CNV</jats:styled-content> formation was analysed. One eye of each <jats:styled-content style="fixed-case">CD</jats:styled-content>11b‐<jats:styled-content style="fixed-case">HSVTK</jats:styled-content> mouse was injected with <jats:styled-content style="fixed-case">GCV</jats:styled-content>, 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 (<jats:styled-content style="fixed-case">CNV</jats:styled-content>) was induced by argon laser and analysed at day 14.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The most effective <jats:styled-content style="fixed-case">CD</jats:styled-content>11b<jats:sup>+</jats:sup> cell depletion was achieved 7 days after a single injection and 14 days after two injections of <jats:styled-content style="fixed-case">GCV</jats:styled-content>. After two injections of <jats:styled-content style="fixed-case">GCV</jats:styled-content>, we found a significant reduction of <jats:styled-content style="fixed-case">CD</jats:styled-content>11b<jats:sup>+</jats:sup> cells in central (52 ± 23.9 cells/mm<jats:sup>2</jats:sup>) and peripheral retina (53 ± 20.6 cells/mm<jats:sup>2</jats:sup>); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm<jats:sup>2</jats:sup>, p &lt; 0.001, respectively). Regarding <jats:styled-content style="fixed-case">CNV</jats:styled-content> areas, no statistical significance was found between the groups.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The <jats:styled-content style="fixed-case">CD</jats:styled-content>11b‐<jats:styled-content style="fixed-case">HSVTK</jats:styled-content> mouse is a feasible model for a local depletion of <jats:styled-content style="fixed-case">CD</jats:styled-content>11b<jats:sup>+</jats:sup> cells in the retina. Nevertheless, only a partial depletion of <jats:styled-content style="fixed-case">CD</jats:styled-content>11b<jats:sup>+</jats:sup> cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in <jats:styled-content style="fixed-case">CNV</jats:styled-content> areas. In the light of previous knowledge, the potential influence of systemic immune cells on <jats:styled-content style="fixed-case">CNV</jats:styled-content> formation might be more relevant than expected.</jats:p></jats:sec>
  • Access State: Open Access