Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny

被引：31

作者：

Beaudry-Richard, Alexandra ^{[1
,2
,3
]}

Nadeau-Vallee, Mathieu ^{[1
,2
,3
,4
]}

Prairie, Elizabeth ^{[1
,2
,3
]}

Maurice, Noemie ^{[1
,2
,3
]}

Heckel, Emilie ^{[1
,2
,3
]}

Nezhady, Mohammad ^{[1
,2
,3
]}

Pundir, Sheetal ^{[1
,2
,3
]}

Madaan, Ankush ^{[1
,2
,3
,5
]}

Boudreault, Amarilys ^{[1
,2
,3
]}

Hou, Xin ^{[1
,2
,3
]}

Quiniou, Christiane ^{[1
,2
,3
]}

Sierra, Estefania Marin ^{[1
,2
,3
,5
]}

Beaulac, Alexandre ^{[1
,2
,3
]}

Lodygensky, Gregory ^{[1
,2
,3
]}

Robertson, Sarah A. ^{[6
]}

Keelan, Jeffrey ^{[7
]}

Adams-Waldorf, Kristina ^{[8
]}

Olson, David M. ^{[9
,10
,11
]}

Rivera, Jose-Carlos ^{[12
]}

Lubell, William D. ^{[13
]}

Joyal, Jean-Sebastien ^{[1
,2
,3
,4
,5
]}

Bouchard, Jean-Francois ^{[14
]}

Chemtob, Sylvain ^{[1
,2
,3
,4
,5
]}

机构：

[1] CHU St Justine Res Ctr, Dept Pediat, Montreal, PQ, Canada

[2] CHU St Justine Res Ctr, Dept Ophthalmol, Montreal, PQ, Canada

[3] CHU St Justine Res Ctr, Dept Pharmacol, Montreal, PQ, Canada

[4] Univ Montreal, Dept Pharmacol, Montreal, PQ, Canada

[5] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada

[6] Univ Adelaide, Dept Obstet & Gynaecol, Adelaide, SA 5005, Australia

[7] Univ Western Australia, Div Obstet & Gynaecol, King Edward Mem Hosp, Perth, WA, Australia

[8] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA

[9] Univ Alberta, Dept Obstet & Gynecol, Edmonton, AB, Canada

[10] Univ Alberta, Dept Pediat, Edmonton, AB, Canada

[11] Univ Alberta, Dept Physiol, Edmonton, AB, Canada

[12] Maisonneuve Rosemont Hosp, Dept Ophthalmol, Res Ctr, Montreal, PQ, Canada

[13] Univ Montreal, Dept Chem, Montreal, PQ, Canada

[14] Univ Montreal, Sch Optometry, Montreal, PQ, Canada

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

加拿大自然科学与工程研究理事会; 美国国家卫生研究院; 加拿大健康研究院; 英国医学研究理事会;

关键词：

PRETERM PRELABOR RUPTURE; GENE POLYMORPHISM; AMNIOTIC-FLUID; CHOROIDAL INVOLUTION; INTERLEUKIN-1; RETINOPATHY; FETAL; ANTAGONIST; INJURY; CELLS;

D O I：

10.1038/s41598-018-30087-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Antenatal inflammation as seen with chorioamnionitis is harmful to foetal/neonatal organ development including to eyes. Although the major pro-inflammatory cytokine IL-1 beta participates in retinopathy induced by hyperoxia (a predisposing factor to retinopathy of prematurity), the specific role of antenatal IL-1 beta associated with preterm birth (PTB) in retinal vasculopathy (independent of hyperoxia) is unknown. Using a murine model of PTB induced with IL-1 beta injection in utero, we studied consequent retinal and choroidal vascular development; in this process we evaluated the efficacy of IL-1R antagonists. Eyes of foetuses exposed only to IL-1 beta displayed high levels of pro-inflammatory genes, and a persistent postnatal infiltration of inflammatory cells. This prolonged inflammatory response was associated with: (1) a marked delay in retinal vessel growth; (2) long-lasting thinning of the choroid; and (3) long-term morphological and functional alterations of the retina. Antenatal administration of IL-1R antagonists -101.10 (a modulator of IL-1R) more so than Kineret (competitive IL-1R antagonist) - prevented all deleterious effects of inflammation. This study unveils a key role for IL-1 beta, a major mediator of chorioamnionitis, in causing sustained ocular inflammation and perinatal vascular eye injury, and highlights the efficacy of antenatal 101.10 to suppress deleterious inflammation.

引用

页数：13

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