scholarly journals Environmental oxygen regulates astrocyte proliferation to guide angiogenesis during retinal development

Development ◽  
2021 ◽  
Vol 148 (9) ◽  
Author(s):  
Robin M. Perelli ◽  
Matthew L. O'Sullivan ◽  
Samantha Zarnick ◽  
Jeremy N. Kay

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.

2019 ◽  
Author(s):  
Robin M Perelli ◽  
Matthew L O’Sullivan ◽  
Samantha Zarnick ◽  
Jeremy N Kay

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.


2017 ◽  
Vol 42 (11) ◽  
pp. 1511-1517
Author(s):  
Chang Sik Cho ◽  
Sang-Mok Lee ◽  
Byung Joo Lee ◽  
Dong Hyun Jo ◽  
Jin Hyoung Kim ◽  
...  

1999 ◽  
Vol 69 (5) ◽  
pp. 511-523 ◽  
Author(s):  
TRENT M. SANDERCOE ◽  
MICHELE C. MADIGAN ◽  
FRANCIS A. BILLSON ◽  
PHILIP L. PENFOLD ◽  
JAN M. PROVIS

2002 ◽  
Vol 76 (7) ◽  
pp. 392-397 ◽  
Author(s):  
Lisa Imamura ◽  
Hiroshi Hasegawa ◽  
Kaori Kurashina ◽  
Tomoya Matsuno ◽  
Masaaki Tsuda

Author(s):  
U.I. Heine ◽  
G.R.F. Krueger ◽  
E. Munoz ◽  
A. Karpinski

Infection of newborn mice with Moloney leukemia virus (M-MuLV) causes a T-cell differentiation block in the thymic cortex accompanied by proliferation and accumulation of prethymic lymphoblasts in the thymus and subsequent spreading of these cells to generate systemic lymphoma. Current evidence shows that thymic reticular epithelial cells (REC) provide a microenvironment necessary for the maturation of prethymic lymphoblasts to mature T-lymphocytes by secretion of various thymic factors. A change in that environment due to infection of REC by virus could be decisive for the failure of lymphoblasts to mature and thus contribute to lymphoma development.We have studied the morphology and distribution of the major thymic cell populations at different stages of tumorigenesis in Balb/c mice infected when newborn with 0.2ml M-MuLV suspension, 6.8 log FFU/ml. Thymic tissue taken at 1-2 weekly intervals up to tumor development was processed for light and electron microscopy, using glutaraldehyde-OsO4fixation and Epon-Araldite embedding.


Author(s):  
C. Uphoff ◽  
C. Nyquist-Battie

Fetal Alcohol Syndrone (FAS) is a syndrome with characteristic abnormalities resulting from prenatal exposure to ethanol. In many children with FAS syndrome gross pathological changes in the heart are seen with septal defects the most prevalent abnormality recorded. Few studies in animal models have been performed on the effects of ethanol on heart development. In our laboratory, it has been observed that prenatal ethanol exposure of Swiss albino mice results in abnormal cardiac muscle ultrastructure when mice were examined at birth and compared to pairfed and normal controls. Fig. 1 is an example of the changes that are seen in the ethanol-exposed animals. These changes include enlarged mitochondria with loss of inner mitochondrial membrane integrity and loss of myofibrils. Morphometric analysis substantiated the presence of these alterations from normal cardiac ultrastructure. The present work was undertaken to determine if the pathological changes seen in the newborn mice prenatally exposed to ethanol could be reversed with age and abstinence.


2005 ◽  
Vol 47 (7) ◽  
pp. 436-436 ◽  
Author(s):  
AD Flouris ◽  
BE Faught ◽  
J Hay ◽  
J Cairney

2006 ◽  
Vol 48 (11) ◽  
pp. 896 ◽  
Author(s):  
Pascale Guillem ◽  
Christine Cans ◽  
Vincent Guinchat ◽  
Marc Ratel ◽  
Pierre-Simon Jouk

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