Etiopathogenesis in Retinopathy of Prematurity

Vascular Endothelial ◽

Retinal Tissue ◽

Oxygen Induced Retinopathy ◽

Weight Suppression ◽

Exogenous Factors ◽

Endothelial Growth Factor ◽

Pathologic Neovascularization

Retinopathy of prematurity is a potentially blinding disease associated with low gestational age and birth weight. Suppression of growth factors due to hyperoxia and loss of maternal-fetal interaction cause impaired development of retinal vascularization. Subsequently, an increase in metabolic demands and inadequate vascularization lead to hypoxia that triggers the pathologic neovascularization process, which may lead to a retinal detachment in retinal tissue. Vascular endothelial growth factor (VEGF) has a key role in both physiologic and pathologic vascularization. Based upon in animal models of oxygen-induced retinopathy (OIR) exogenous factors like oxygen levels, oxidative stress, inflammation and cytokines, several signaling pathways and receptors have been linked to the pathogenesis of retinopathy of prematurity.

Vascular Endothelial Growth Factor Signaling in Models of Oxygen-Induced Retinopathy: Insights Into Mechanisms of Pathology in Retinopathy of Prematurity

Frontiers in Pediatrics ◽

10.3389/fped.2021.796143 ◽

2021 ◽

Vol 9 ◽

Author(s):

Aniket Ramshekar ◽

M. Elizabeth Hartnett

Keyword(s):

Growth Factor ◽

Neuronal Development ◽

Growth Factor Signaling ◽

Vascular Endothelial ◽

Vegf Signaling ◽

Oxygen Induced Retinopathy ◽

Retinal Angiogenesis ◽

Endothelial Growth Factor

Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide. Blindness can occur from retinal detachment caused by pathologic retinal angiogenesis into the vitreous, termed intravitreal neovascularization (IVNV). Although agents that interfere with the bioactivity of vascular endothelial growth factor (VEGF) are now used to treat IVNV, concerns exist regarding the identification of optimal doses of anti-VEGF for individual infants and the effect of broad VEGF inhibition on physiologic angiogenesis in external organs or in the retina of a preterm infant. Therefore, it is important to understand VEGF signaling in both physiologic and pathologic angiogenesis in the retina. In this manuscript, we review the role of receptors that interact with VEGF in oxygen-induced retinopathy (OIR) models that represent features of ROP pathology. Specifically, we discuss our work regarding the regulation of VEGFR2 signaling in retinal endothelial cells to not only reduce severe ROP but also facilitate physiologic retinal vascular and neuronal development.

The Nrf2 inhibitor brusatol has a protective role in a rat model of oxygen-induced retinopathy of prematurity

Visual Neuroscience ◽

10.1017/s095252382100002x ◽

2021 ◽

Vol 38 ◽

Author(s):

Xiuying Liang ◽

Ruifen Wang

Keyword(s):

Growth Factor ◽

Rat Model ◽

Related Factor ◽

Vascular Endothelial ◽

Down Regulation ◽

Oxygen Induced Retinopathy ◽

Vessel Morphology ◽

Endothelial Growth Factor

Abstract Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been testified to be involved in the development of retinopathy of prematurity (ROP), which can cause childhood visual impairment. Whether brusatol, an Nrf2 inhibitor, could be utilized to treat ROP was unknown. The oxygen-induced retinopathy rat model was established to mimic ROP, which was further intravitreal administrated with brusatol. Vessel morphology and microglial activation in the retina were assessed with histology analysis. The relative expression levels of angiogenesis and inflammation-related molecules were detected with Western blot and real-time polymerase chain reaction methods. Intravitreal brusatol administration could alleviate both angiogenesis and microgliosis induced by hyperoxia, along with down-regulation of vascular endothelial growth factor, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, cluster of differentiation molecule 11B, tumor necrosis factor alpha, inducible nitric oxide synthase, glial fibrillary acidic protein, and IBA-1 expression. It was further revealed that Nrf2 and heme oxygenease-1 were diminished by brusatol administration. The results demonstrate the potential of intravitreal brusatol deliver to treat ROP with down-regulation of angiogenesis and microgliosis.

Dynamics of Intraocular Pressure after Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors in Retinopathy of Prematurity

Russian ophthalmology of children ◽

10.25276/2307-6658-2020-2-31-36 ◽

2020 ◽

pp. 31-36

Author(s):

Е.Е. Sidorenko ◽

◽

S.А. Obrubov ◽

Е.I. Sidorenko ◽

N.S. Levina ◽

...

Keyword(s):

Intraocular Pressure ◽

Growth Factor ◽

Intravitreal Injection ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Screening auf Frühgeborenenretinopathie – die wichtigsten Änderungen in der neuen deutschen Leitlinie 2020

Der Ophthalmologe ◽

10.1007/s00347-021-01393-6 ◽

2021 ◽

Author(s):

Jeany Q. Li ◽

Ulrich Kellner ◽

Birgit Lorenz ◽

Andreas Stahl ◽

Tim U. Krohne

Keyword(s):

Growth Factor ◽

Vascular Endothelial ◽

Anti Vegf ◽

Zone Ii ◽

Endothelial Growth Factor ◽

Rop Screening

Zusammenfassung Hintergrund Durch Verbesserungen in der neonatologischen Versorgung von Frühgeborenen und die Entwicklung neuer Behandlungsmöglichkeiten der Frühgeborenenretinopathie („retinopathy of prematurity“ [ROP]) haben sich die Anforderungen an das ROP-Screening seit der Veröffentlichung der letzten Fassung der deutschen Leitlinie zum ROP-Screening im Jahr 2008 verändert. Auf Grundlage aktueller Studiendaten wurde die Leitlinie in 2020 grundlegend überarbeitet und in einer aktualisierten Fassung veröffentlicht. Ziel Dieser Artikel fasst die wichtigsten Änderungen in der neuen Leitlinie zusammen. Ergebnisse Die Altersgrenze für einen Screeningeinschluss wurde für Kinder ohne zusätzliche Risikofaktoren auf ein Gestationsalter von unter 31 Wochen gesenkt. Die Mindestdauer für eine Sauerstoffsupplementation, die einen Einschluss in das Screening bei Frühgeborenen erforderlich macht, wurde auf über 5 Tage angehoben. Eine Behandlung bei ROP in Zone II kann nun schon bei jedem Stadium 3 mit Plus-Symptomatik unabhängig von der Anzahl der betroffenen Uhrzeiten erfolgen. Für die Nachkontrollen nach Anti-VEGF („vascular endothelial growth factor“)-Therapie wurden Kriterien zur Frequenz und Dauer definiert. Das verbindliche Dokument für diese und weitere neue Empfehlungen ist die Leitlinie selber. Schlussfolgerungen Die Empfehlungen der Leitlinie ermöglichen eine zuverlässige Identifikation von Kindern mit ROP-Risiko für den Einschluss in das Screening und eine rechtzeitige Erkennung fortgeschrittener Krankheitsstadien für die Therapieeinleitung, um so Erblindung durch ROP zu verhindern.