Systemic Inflammation Perturbs Developmental Retinal Angiogenesis and Neuroretinal Function

Tremblay, Sophie; Miloudi, Khalil; Chaychi, Samaneh; Favret, Sandra; Binet, François; Polosa, Anna; Lachapelle, Pierre; Chemtob, Sylvain; Sapieha, Przemysław

doi:10.1167/iovs.13-12496

Cited by 80 publications

(71 citation statements)

References 66 publications

(93 reference statements)

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“…Inflammation has also been associated with ROP both in the ELGAN cohort 50 and in other studies 51–53 . An inflammatory contribution to the occurrence of VFD is in keeping with animal models that document that systemic inflammation can affect white matter development 54 , and retinal development 55 .…”

Section: Discussionsupporting

confidence: 67%

Antecedents and correlates of visual field deficits in children born extremely preterm

Holm

Msall

Skranes

et al. 2015

European Journal of Paediatric Neurology

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Aim We sought to identify the antecedents and correlates of visual field deficits (VFDs) at age 2 years among infants born before the 28th week of gestation. Methods The visual fields of 1023 infants were assessed by confrontation at age 2 years. We compared the ante-and postnatal characteristics and exposures of the 65 infants with a VFD to their peers who did not have a VFD. We used time-oriented logistic regression risk models to assess the associations of potential antecedents and correlates with a VFD. Results In the final regression model, VFD was associated with maternal consumption of aspirin during the current pregnancy, recurring/persistent acidemia during the first 3 postnatal days, cerebral ventriculomegaly seen on neonatal ultrasound, prethreshold retinopathy of prematurity (ROP), and supplemental oxygen and ventilator dependence at 36 weeks post-menstrual age. Birth before the 27th week was also associated with increased risk, but its significance was diminished by the addition of postnatal variables. Conclusion In this sample of extremely preterm born infants, antenatal as well as early and late postnatal characteristics and exposures are associated with an increased risk of having a VFD. Our study adds to our knowledge about the complex etiology of visual deficits of prematurity, and supports a multifactorial cause of these deficits.

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Section: Discussionsupporting

confidence: 67%

Antecedents and correlates of visual field deficits in children born extremely preterm

Holm

Msall

Skranes

et al. 2015

European Journal of Paediatric Neurology

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“…In addition to clinical observations, Tremblay et al . [30] recently reported that perinatal LPS-induced inflammation without concurrent oxygen manipulation perturbed vascular development in the developing mouse retina. They observed an early increase in retinal vascular density and late depletion of retinal vascular beds in neonatal mice after systemic LPS administration.…”

Section: Discussionmentioning

confidence: 99%

“…Tremblay et al . [30] injected LPS once at P4, whereas we injected LPS three times at P1, P3, and P5. Thus, it is possible that the early and sustained inflammation in our model triggered more severe aberration in retinal vessel development similar to ROP.…”

Section: Discussionmentioning

confidence: 99%

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Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity

Hong

Lee

et al. 2014

J Neuroinflammation

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BackgroundAlteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats.MethodsTo induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis.ResultsWe found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located.ConclusionsOur data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP.

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“…This is evident in the retina, in which an intensified, largely microglial/macrophage-based immune response is associated with the progression of several sight-threatening diseases, such as diabetic retinopathy (DR) (3)(4)(5), age-related macular degeneration (AMD) (6)(7)(8), and retinopathy of prematurity (ROP) (9,10). Together, these retinal diseases account for the principal causes of loss of sight in industrialized countries (6,11,12).…”

Section: Introductionmentioning

confidence: 99%

Neuropilin-1 mediates myeloid cell chemoattraction and influences retinal neuroimmune crosstalk

Dejda¹,

Mawambo²,

Cerani³

et al. 2014

J. Clin. Invest.

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Systemic Inflammation Perturbs Developmental Retinal Angiogenesis and Neuroretinal Function

Cited by 80 publications

References 66 publications

Antecedents and correlates of visual field deficits in children born extremely preterm

Antecedents and correlates of visual field deficits in children born extremely preterm

Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity

Neuropilin-1 mediates myeloid cell chemoattraction and influences retinal neuroimmune crosstalk

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