1. Stabilization of myeloid-derived HIFs promotes vascular regeneration in retinal ischemia
- Author
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Robin R. Ali, Maeve Barlow, James W B Bainbridge, Enrico Cristante, Sidath E. Liyanage, Yanai Duran, Pilar Villacampa, Katja E. Menger, Laura Abelleira-Hervas, Izabela P Klaska, Robert D. Sampson, Ulrich F O Luhmann, and Alexander J. Smith
- Subjects
Vascular Endothelial Growth Factor A ,0301 basic medicine ,Cancer Research ,genetic structures ,Physiology ,Angiogenesis ,Clinical Biochemistry ,Mice, Transgenic ,Brief Communication ,Retina ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Retinal Diseases ,Ischemia ,Vhl ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,HIF ,Animals ,Regeneration ,Diabetic Retinopathy ,business.industry ,Regeneration (biology) ,Retinal Vessels ,Retinal ,Retinopathy of prematurity ,Diabetic retinopathy ,OIR ,Macular degeneration ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Vascular regeneration ,Cell Hypoxia ,eye diseases ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Animals, Newborn ,chemistry ,Von Hippel-Lindau Tumor Suppressor Protein ,Myeloid cells ,Cancer research ,sense organs ,business ,030217 neurology & neurosurgery ,Retinopathy - 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. Electronic supplementary material The online version of this article (10.1007/s10456-019-09681-1) contains supplementary material, which is available to authorized users.
- Published
- 2019
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