Astrocyte Proliferation During Development of the Human Retinal Vasculature

AbstractAngiogenesis 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 hyperoxia – disrupts formation of the angiogenic astrocyte template. Exposing mice to hyperoxia (75% O2) from postnatal day (P)0-4 suppressed astrocyte proliferation, while return to room air (21% O2) at P4 triggered extensive proliferation, massively increasing astrocyte numbers and disturbing their spatial patterning prior to arrival of developing vasculature. Proliferation required astrocytic HIF2α and was also stimulated by direct hypoxia (10% O2), 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.

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Environmental oxygen regulates astrocyte proliferation to guide angiogenesis during retinal development

Development ◽

10.1242/dev.199418 ◽

2021 ◽

Vol 148 (9) ◽

Author(s):

Robin M. Perelli ◽

Matthew L. O'Sullivan ◽

Samantha Zarnick ◽

Jeremy N. Kay

Keyword(s):

Developmental Disorders ◽

Excess Oxygen ◽

Neonatal Exposure ◽

Retinal Vasculature ◽

Molecular Pathways ◽

Spatial Patterning ◽

Newborn Mice ◽

Astrocyte Proliferation ◽

Mammalian Retina ◽

Retinal Angiogenesis

ABSTRACT 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.

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Immature Retinal Vasculature in Zone 3

10.32388/8mwgoo ◽

2020 ◽

Author(s):

Keyword(s):

Retinal Vasculature

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Fenofibrate Increases Heme Oxygenase 1 Expression and Astrocyte Proliferation While Limits Neuronal Injury During Intracerebral Hemorrhage

Current Neurovascular Research ◽

10.2174/1567202613666161014161943 ◽

2017 ◽

Vol 14 (1) ◽

pp. 11-18 ◽

Cited By ~ 7

Author(s):

Yan Wang ◽

Min Yu ◽

Yue Ma ◽

Ruoping Wang ◽

Wei Liu ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Heme Oxygenase ◽

Neuronal Injury ◽

Heme Oxygenase 1 ◽

Astrocyte Proliferation

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The effect of insulin pump therapy in retinal vasculature in type 1 diabetic patients

European Journal of Ophthalmology ◽

10.1177/1120672121990576 ◽

2021 ◽

pp. 112067212199057

Author(s):

Tomás de Oliveira Loureiro ◽

João Nobre Cardoso ◽

Carlos Diogo Pinheiro Lima Lopes ◽

Ana Rita Carreira ◽

Sandra Rodrigues-Barros ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Metabolic Control ◽

Insulin Pump Therapy ◽

Vascular Density ◽

Diabetic Patients ◽

Retinal Vasculature ◽

Increased Risk ◽

The Mean ◽

Type 1 Diabetic Patients

Background/objectives: Continuous subcutaneous insulin infusion (CSII) is a treatment for type 1 diabetes that improves metabolic control and reduces micro and macrovascular complications. The aim of this study was to compare the effect of CSII versus traditional multiple daily injections (MDI) therapy on retinal vasculature. Methods: We performed a prospective study with type 1 diabetic patients with no prior history of ocular pathology other than mild diabetic retinopathy. The patients were divided into two groups according to their therapeutic modality (CSII vs MDI). The retinal nerve fiber layers thickness and vascular densities were compared between groups in both macula and optic disc. The correlations between vascular density and clinical features were also determined. Statistical significance was defined as p < 0.05. Results: The study included 52 eyes, 28 in the insulin CSII group. The mean age was 36.66 ± 12.97 years, with no difference between groups ( p = 0.49). The mean glycated hemoglobin (HbA1c) was found to be lower in the CSII group (7.1% ± 0.7 vs 7.5% ± 0.7 p < 0.01). The parafoveal vascular density was found to be higher in the CSII group (42.5% ± 0.4 vs 37.7% ± 0.6, p < 0.01). We found an inverse correlation between HbA1c value and parafoveal vascular densities ( p < 0.01, r = −0.50). Conclusion: We found that CSII provided better metabolic control than MDI and this seemed to result in higher parafoveal vascular density. As lower vascular density is associated with an increased risk of diabetic retinopathy, these results suggest that CSII could be the safest therapeutic option to prevent retinopathy.

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Response to the effect of pharmacologic treatment of migraine on retinal vasculature

European Journal of Ophthalmology ◽

10.1177/11206721211028042 ◽

2021 ◽

pp. 112067212110280

Author(s):

Julio González-Martín-Moro ◽

Jesús Porta Etessam ◽

Belén Pilo de la Fuente ◽

Irene Fuentes Vega ◽

Inés Contreras

Keyword(s):

Retinal Vasculature ◽

Pharmacologic Treatment

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Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-026 ◽

1994 ◽

Vol 72 (2) ◽

pp. 168-173 ◽

Cited By ~ 27

Author(s):

Daniel Abran ◽

Daya R. Varma ◽

Ding-You Li ◽

Sylvain Chemtob

Keyword(s):

Blood Flow ◽

Receptor Agonist ◽

Perfusion Pressure ◽

Retinal Blood Flow ◽

Receptor Subtype ◽

Retinal Vasculature ◽

Receptor Subtypes ◽

Retinal Vessels ◽

Limit Blood Flow ◽

Arteries And Veins

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2α, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2α and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2α and PGE2, the thromboxane analogue, U46619, as well as the α1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult. Our findings indicate that the retinal vasculature of the newborn responds minimally to prostaglandins, primarily PGF2α and PGE2, compared with the adult, but constricts effectively to thromboxane. Since prostaglandins play an important role in the autoregulation of retinal blood flow, our observations provide an explanation for the inability of the newborn to limit blood flow when perfusion pressure is raised.Key words: retinal vascular responses, prostaglandins, thromboxane, PGE2 receptor subtypes.

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