| First Author | Yamaguchi M | Year | 2022 |
| Journal | Diabetes | Volume | 71 |
| Issue | 12 | Pages | 2685-2701 |
| PubMed ID | 36203331 | Mgi Jnum | J:341437 |
| Mgi Id | MGI:7539613 | Doi | 10.2337/db21-0247 |
| Citation | Yamaguchi M, et al. (2022) Identifying Hyperreflective Foci in Diabetic Retinopathy via VEGF-Induced Local Self-Renewal of CX3CR1+ Vitreous Resident Macrophages. Diabetes 71(12):2685-2701 |
| abstractText | Intraretinal hyperreflective foci (HRF) are significant biomarkers for diabetic macular edema. However, HRF at the vitreoretinal interface (VRI) have not been examined in diabetic retinopathy (DR). A prospective observational clinical study with 162 consecutive eyes using OCT imaging showed significantly increased HRF at the VRI during DR progression (P < 0.01), which was reversed by anti-vascular endothelial growth factor (VEGF) therapy. F4/80+ macrophages increased significantly at the VRI in Kimba (vegfa+/+) or Akimba (Akita x Kimba) mice (both P < 0.01), but not in diabetic Akita (Ins2+/-) mice, indicating macrophage activation was modulated by elevated VEGF rather than the diabetic milieu. Macrophage depletion significantly reduced HRF at the VRI (P < 0.01). Furthermore, BrdU administration in Ccr2rfp/+Cx3cr1gfp/+vegfa+/- mice identified a significant contribution of M2-like tissue-resident macrophages (TRMs) at the VRI. Ki-67+ and CD11b+ cells were observed in preretinal tissues of DR patients, while exposure of vitreal macrophages to vitreous derived from PDR patients induced a significant proliferation response in vitro (P < 0.01). Taken together, the evidence suggests that VEGF drives a local proliferation of vitreous resident macrophages (VRMs) at the VRI during DR. This phenomenon helps to explain the derivation and disease-relevance of the HRF lesions observed through OCT imaging in patients. |
