Retinal microglia are critical for subretinal neovascular formation
| Autor: | Yoshihiko Usui, Michael I. Dorrell, Toshihide Kurihara, Martin Friedlander, Ayumi Usui-Ouchi, Stephen Bravo, Yoichiro Ideguchi, Susumu Sakimoto, Edith Aguilar |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty genetic structures Retinal Pigment Epithelium Retinal Neovascularization Retina Pathogenesis Neovascularization 03 medical and health sciences chemistry.chemical_compound Macular Degeneration 0302 clinical medicine Medicine Animals Macular telangiectasia Mice Knockout Microglia medicine.diagnostic_test Neovascularization Pathologic business.industry Retinal Vessels Retinal General Medicine medicine.disease eye diseases Vascular endothelial growth factor A Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis sense organs medicine.symptom business Retinopathy Electroretinography Research Article |
| Zdroj: | JCI Insight |
| ISSN: | 2379-3708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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