Environmental oxygen regulates astrocyte proliferation to guide angiogenesis during retinal development
| Autor: | Robin M. Perelli, Samantha Zarnick, Matthew L. O'Sullivan, Jeremy N. Kay |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Mouse
Angiogenesis Neovascularization Physiologic chemistry.chemical_element Development Biology Oxygen Retina Retinopathy of prematurity Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Oxygen-induced retinopathy Hypoxia Transcription factor Molecular Biology Cell Proliferation 030304 developmental biology Hyperoxia 0303 health sciences Neovascularization Pathologic Retinal Vessels Retinal Hypoxia (medical) medicine.disease Phenotype Cell biology medicine.anatomical_structure Animals Newborn chemistry Astrocytes 030221 ophthalmology & optometry Neural Development Female medicine.symptom Astrocyte 030217 neurology & neurosurgery Research Article Retinopathy Developmental Biology |
| Zdroj: | Development (Cambridge, England) article-version (VoR) Version of Record |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | Angiogenesis in the developing mammalian retina requires patterning cues from astrocytes. Developmental disorders of retinal vasculature, such as retinopathy of prematurity (ROP), involve arrest or mispatterning of angiogenesis. Whether these vascular pathologies involve astrocyte dysfunction remains untested. Here, we demonstrate that the major risk factor for ROP – transient neonatal exposure to excess oxygen – disrupts formation of the angiogenic astrocyte template. Exposing newborn mice to elevated oxygen (75%) suppressed astrocyte proliferation, whereas return to room air (21% oxygen) at postnatal day 4 triggered extensive proliferation, massively increasing astrocyte numbers and disturbing their spatial patterning prior to the arrival of developing vasculature. Proliferation required astrocytic HIF2α and was also stimulated by direct hypoxia (10% oxygen), suggesting that astrocyte oxygen sensing regulates the number of astrocytes produced during development. Along with astrocyte defects, return to room air also caused vascular defects reminiscent of ROP. Strikingly, these vascular phenotypes were more severe in animals that had larger numbers of excess astrocytes. Together, our findings suggest that fluctuations in environmental oxygen dysregulate molecular pathways controlling astrocyte proliferation, thereby generating excess astrocytes that interfere with retinal angiogenesis. Highlighted Article: Oxygen regulates proliferation of immature retinal astrocytes. Perturbing this mechanism inflates astrocyte numbers, disrupts retinal angiogenesis and leads to vascular pathologies resembling retinopathy of prematurity. |
| Databáze: | OpenAIRE |
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