Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption

Autor: Amani A. Fawzi, Ronil S. Shah, Herminio J. Cardona, Kathryn N. Farrow, Michelle Lajko, Joann M. Taylor
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Retinal Ganglion Cells
Vascular Endothelial Growth Factor A
Pathology
Angiogenesis
Physiology
Glycobiology
Gene Expression
lcsh:Medicine
Retinal Neovascularization
Cardiovascular Physiology
Biochemistry
chemistry.chemical_compound
Mice
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
lcsh:Science
Hyperoxia
Neurons
Multidisciplinary
Membrane Glycoproteins
Retinal detachment
Retinopathy of prematurity
Immunohistochemistry
3. Good health
Vascular endothelial growth factor A
Chemistry
medicine.anatomical_structure
NADPH Oxidase 2
Physical Sciences
Retinal Disorders
Collagen
medicine.symptom
Anatomy
Cellular Types
Research Article
Chemical Elements
medicine.medical_specialty
Ganglion Cells
Ocular Anatomy
Biology
Retina
03 medical and health sciences
Ocular System
medicine
Animals
Humans
Glycoproteins
Vitreoretinopathy
Proliferative
lcsh:R
Retinitis
Retinal Detachment
NADPH Oxidases
Retinal Vessels
Biology and Life Sciences
Fibrinogen
Afferent Neurons
Retinal
Cell Biology
medicine.disease
Hypoxia-Inducible Factor 1
alpha Subunit
Vascular Endothelial Growth Factor Receptor-2
Surgery
Oxygen
Disease Models
Animal
Ophthalmology
030104 developmental biology
chemistry
Bronchopulmonary dysplasia
Cellular Neuroscience
030221 ophthalmology & optometry
Cardiovascular Anatomy
Blood Vessels
lcsh:Q
Developmental Biology
Neuroscience
Zdroj: PLoS ONE, Vol 11, Iss 11, p e0166886 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: Bronchopulmonary dysplasia (BPD) is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR), shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P)0 to P14 to model BPD, then allowed to recover in room air for 1 (P15), 7 (P21), or 14 days (P28). We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80) and lymphocytes (CD45R). Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment.
Databáze: OpenAIRE
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