Retinal microglia are critical for subretinal neovascular formation

Ayumi Usui-Ouchi, Yoshihiko Usui, Toshihide Kurihara, Edith Aguilar, Michael I. Dorrell, Yoichiro Ideguchi, Susumu Sakimoto, Stephen Bravo, Martin Friedlander

Research output: Contribution to journalArticle

Abstract

Abnormal subretinal neovascularization is a characteristic of vision-threatening retinal diseases, including macular telangiectasia (MacTel) and retinal angiomatous proliferation (RAP). Subretinal neovascular tufts and photoreceptor dysfunction are observed in very-low-density lipoprotein receptor (Vldlr-/-) mutant mice. These changes mirror those observed in patients with MacTel and RAP, but the pathogenesis is largely unknown. In this study, we show that retinal microglia were closely associated with retinal neovascular tufts in Vldlr-/- mice and retinal tissue from patients with MacTel; ablation of microglia/macrophages dramatically prevented formation of retinal neovascular tufts and improved neuronal function, as assessed by electroretinography. Vldlr-/- mice with retinal pigmented epithelium-specific (RPE-specific) Vegfa had greatly reduced subretinal infiltration of microglia/macrophages, subsequently reducing neovascular tufts. These findings highlight the contribution of microglia/macrophages to the pathogenesis of neovascularization, provide valuable clues regarding potential causative cellular mechanisms for subretinal neovascularization in patients with MacTel and RAP and suggest that targeting microglia activation may be a therapeutic option in these diseases.

Original languageEnglish
JournalJCI Insight
Volume5
Issue number12
DOIs
Publication statusPublished - 2020 Jun 18

Keywords

  • Angiogenesis
  • Ophthalmology
  • Retinopathy

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Usui-Ouchi, A., Usui, Y., Kurihara, T., Aguilar, E., Dorrell, M. I., Ideguchi, Y., Sakimoto, S., Bravo, S., & Friedlander, M. (2020). Retinal microglia are critical for subretinal neovascular formation. JCI Insight, 5(12). https://doi.org/10.1172/jci.insight.137317