1. Stabilization of myeloid-derived HIFs promotes vascular regeneration in retinal ischemia.
- Author
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Villacampa, Pilar, Liyanage, Sidath E., Klaska, Izabela P., Cristante, Enrico, Menger, Katja E., Sampson, Robert D., Barlow, Maeve, Abelleira-Hervas, Laura, Duran, Yanai, Smith, Alexander J., Ali, Robin R., Luhmann, Ulrich F. O., and Bainbridge, James W. B.
- Subjects
RETROLENTAL fibroplasia ,OPTICAL interference ,DIABETIC retinopathy ,RETINAL degeneration ,NEOVASCULARIZATION - Abstract
The retinal vasculature is tightly organized in a structure that provides for the high metabolic demand of neurons while minimizing interference with incident light. The adverse impact of retinal vascular insufficiency is mitigated by adaptive vascular regeneration but exacerbated by pathological neovascularization. Aberrant growth of neovessels in the retina is responsible for impairment of sight in common blinding disorders including retinopathy of prematurity, proliferative diabetic retinopathy, and age-related macular degeneration. Myeloid cells are key players in this process, with diverse roles that can either promote or protect against ocular neovascularization. We have previously demonstrated that myeloid-derived VEGF, HIF1, and HIF2 are not essential for pathological retinal neovascularization. Here, however, we show by cell-specific depletion of Vhl in a mouse model of retinal ischemia (oxygen-induced retinopathy, OIR) that myeloid-derived HIFs promote VEGF and bFGF expression and enhance vascular regeneration in association with improved density and organization of the astrocytic network. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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