Effects of Marginal Hypoxemia on Recovery from Oxygen-Induced Retinopathy in the Kitten Model

Prolonged oxygen administration in premature infants is the most predictive variable for severe retinopathy of prematurity, after degree of prematurity itself. It was noted that infants receiving prolonged oxygen supplementation are probably hypoxemic relative to their healthy counterparts. Therefore, hypoxemia during recovery from a hyperoxic-induced retinal vascular injury was tested in the kitten model of oxygen-induced retinopathy. Twelve litters were exposed to 80% inspired O2 for 65 hours on day 3, and recovered in room air, 13% or 17% oxygen. The retinas were scored at 4 weeks, and 13% oxygen recovery (PO2 = 39 ± 18 torr) was found to worsen significantly the retinopathy compared with that in room air-recovered littermates (P < .01). Hemorrhages occurred more frequently in the retinas from the hypoxemic-recovered kittens. Clinical trials of this hypothesis are indicated in humans.

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Hyperoxia Inhibits Proliferation of Retinal Endothelial Cells in a Myc-Dependent Manner

Life ◽

10.3390/life11070614 ◽

2021 ◽

Vol 11 (7) ◽

pp. 614

Author(s):

Charandeep Singh ◽

Andrew Benos ◽

Allison Grenell ◽

Sujata Rao ◽

Bela Anand-Apte ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Endothelial Cells ◽

Premature Infants ◽

Endothelial Cell Proliferation ◽

Dependent Manner ◽

Oxygen Supplementation ◽

Retinal Endothelial Cells ◽

Oxygen Induced Retinopathy ◽

Retinal Endothelial Cell

Oxygen supplementation is necessary to prevent mortality in severely premature infants. However, the supraphysiological concentration of oxygen utilized in these infants simultaneously creates retinovascular growth attenuation and vasoobliteration that induces the retinopathy of prematurity. Here, we report that hyperoxia regulates the cell cycle and retinal endothelial cell proliferation in a previously unknown Myc-dependent manner, which contributes to oxygen-induced retinopathy.

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Hyperoxia inhibits proliferation of retinal endothelial cells in Myc dependent manner

10.1101/2020.11.09.375220 ◽

2020 ◽

Author(s):

Charandeep Singh ◽

Andrew Benos ◽

Allison Grenell ◽

Sujata Rao ◽

Bela Anand-Apte ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Endothelial Cells ◽

Premature Infants ◽

Endothelial Cell Proliferation ◽

Dependent Manner ◽

Oxygen Supplementation ◽

Retinal Endothelial Cells ◽

Oxygen Induced Retinopathy ◽

Retinal Endothelial Cell

AbstractOxygen supplementation is necessary to prevent mortality of severely premature infants. However, the supraphysiological concentration of oxygen utilized in these infants simultaneously creates retinovascular growth attenuation and vasoobliteration that induces retinopathy of prematurity. Here, we report that hyperoxia regulates the cell cycle and retinal endothelial cell proliferation in a previously unknown Myc dependent manner which contributes to oxygen-induced retinopathy.

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Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes

Scientific Reports ◽

10.1038/s41598-021-83552-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sang Jin Kim ◽

◽

Kemal Sonmez ◽

Ryan Swan ◽

J. Peter Campbell ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Preterm Infants ◽

Premature Infants ◽

Retinopathy Of Prematurity ◽

Smooth Endoplasmic Reticulum ◽

Enrichment Analysis ◽

Retinal Disease ◽

Gene Set Enrichment Analysis ◽

Whole Exome

AbstractRetinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.

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Daily oxygen supplementation and risk of retinopathy of prematurity

Journal of American Association for Pediatric Ophthalmology and Strabismus ◽

10.1016/j.jaapos.2021.08.223 ◽

2021 ◽

Vol 25 (4) ◽

pp. e59

Author(s):

Marcela M. Estrada ◽

Lauren A. Tomlinson ◽

Yinxi Yu ◽

Gui-shuang Ying ◽

Gil Binenbaum

Keyword(s):

Retinopathy Of Prematurity ◽

Oxygen Supplementation ◽

Risk Of Retinopathy

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Development of a Retinopathy of Prematurity Activity Scale and Clinical Outcome Measures for Use in Clinical Trials

JAMA Ophthalmology ◽

10.1001/jamaophthalmol.2018.5984 ◽

2019 ◽

Vol 137 (3) ◽

pp. 305 ◽

Cited By ~ 6

Author(s):

Lois E. H. Smith ◽

Ann Hellström ◽

Andreas Stahl ◽

Alistair Fielder ◽

Wiley Chambers ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Outcome ◽

Outcome Measures ◽

Retinopathy Of Prematurity ◽

Activity Scale

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The Discovery of Retrolental Fibroplasia and the Role of Oxygen: A Historical Review, 1942–1956

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.23.2.31 ◽

2004 ◽

Vol 23 (2) ◽

pp. 31-38 ◽

Cited By ~ 10

Author(s):

Elizabeth Reedy

Keyword(s):

Premature Infants ◽

Retinopathy Of Prematurity ◽

Historical Review ◽

Retrolental Fibroplasia ◽

History Of ◽

To Come ◽

The 1960S ◽

Prematurely Born Infants ◽

The U.S

Nearly 50 years after it was thought to be conquered, retinopathy of prematurity (ROP) continues to cause vision disturbances and blindness among prematurely born infants. During the 1940s and early 1950s, researchers and caregivers first identified and struggled to eliminate this problem, which seemed to come from nowhere and was concentrated among the most advanced premature nurseries in the U.S. Research studies initially identified many potential causes, none of which could be proved conclusively. By the mid-1950s, oxygen was identified as the culprit, and its use was immediately restricted. The rate of blindness among premature infants decreased significantly. ROP was not cured, however. By the 1960s, it had reappeared. The history of ROP serves to remind us that, despite our best intentions, the care and treatment of premature newborns will always carry with it the possibility of iatrogenic disease. This caution is worth remembering as we work to expand the quality and quantity of clinical research.

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Screening premature infants for retinopathy of prematurity in a tertiary hospital in Saudi Arabia

Annals of Saudi Medicine ◽

10.5144/0256-4947.2020.87 ◽

2020 ◽

Vol 40 (2) ◽

pp. 87-93 ◽

Cited By ~ 1

Author(s):

Enas Mgharbil ◽

Lina Hassan Raffa ◽

Sara Alessa ◽

Aliaa Alamri

Keyword(s):

Saudi Arabia ◽

Premature Infants ◽

Retinopathy Of Prematurity ◽

Tertiary Hospital

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Tocopherol Efficacy and Safety for Preventing Retinopathy of Prematurity: A Randomized, Controlled, Double-Masked Trial

PEDIATRICS ◽

10.1542/peds.79.4.489 ◽

1987 ◽

Vol 79 (4) ◽

pp. 489-500 ◽

Cited By ~ 1

Author(s):

Dale L. Phelps ◽

Arthur L. Rosenbaum ◽

Sherwin J. lsenberg ◽

Rosemary D. Leake ◽

Frederick J. Dorey

Keyword(s):

Premature Infants ◽

Retinopathy Of Prematurity ◽

Plasma Levels ◽

Late Onset ◽

Retinal Hemorrhage ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Late Onset Sepsis ◽

Prospective Monitoring

To test the efficacy and safety of vitamin E in preventing retinopathy of prematurity, 287 infants with birth weights of less than 1.5 kg or gestational ages of less than 33 weeks were enrolled within 24 hours of birth in a randomized, double-masked trial of IV, followed by oral, placebo v tocopherol (adjusted to plasma levels of 3 to 3.5 mg/dL). In the 196 infants completing ophthalmic follow-up, tocopherol did not prevent retinopathy of prematurity of any stage (28% placebo treated v 26% tocopherol treated) or moderately severe retinopathy of prematurity (8% placebo treated v 11% tocopherol treated). Cicatricial sequelae were not significantly different (1/97 placebo treated v 3/99 tocopherol treated), with one placebo-treated infant and one tocopherol-treated infant having retinal detachments. Among all 232 infants examined, those treated with tocopherol had more retinal hemorrhage than placebo-treated infants (8/121 placebo treated v 16/111 tocopherol treated), and retinal hemorrhage correlated positively (P < .01) with plasma levels of tocopherol after the first 2 weeks of age. Prospective monitoring of morbidity including late-onset sepsis, necrotizing enterocolitis, etc revealed no differences between groups except that grades 3 and 4 intraventricular hemorrhage occurred more frequently in infants weighing less than 1 kg at birth who had received tocopherol (14/42, 33%) v those who had received placebo (4/43, 9%) (P < .02). Our data do not support the use of tocopherol for prophylaxis against retinopathy of prematurity in premature infants and suggest that IV tocopherol treatment starting on day 1 may increase the incidence of hemorrhagic complications of prematurity, particularly in infants with birth weights of less than 1 kg.

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