Retinopathy of Prematurity: Current Concepts in Molecular Pathogenesis

Heidary, Gena; VanderVeen, Deborah K.; Smith, Lois E.H.

doi:10.1080/08820530902800314

Cited by 76 publications

(58 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Méhen belül a magzatban 30-50 Hgmm-es artériásvér-oxigéntenzió mellett zajlik a programozott vasculogenesis, amelyet az idő előtti megszületés drá-maian megzavar, a levegő 21%-os oxigénkoncentrációja 85-98 Hgmm-es parciális oxigénnyomást okoz [3]. A hyperoxia, a növekedési faktorok csökkenése a fejlődő retinaerekre káros, megáll a növekedésük, sőt apoptózisba mennek át [4,5,6]. Ez a ROP első fázisa közvetlenül a megszületés után következik be (3. táblá-zat).…”

Section: Retinopathia Prematurorum (Rop)unclassified

Chronic morbidities of premature newborns

Balla

Szabó

2013

Orvosi Hetilap

View full text Add to dashboard Cite

A retinopathia prematurorum, a bronchopulmonalis dysplasia, az intraventricularis haemorrhagia és a periventricularis leukomalacia a koraszülöttek legfontosabb krónikus utóbetegségei, amelyek alapvetően befolyásolják a gyermekek életminőségét. Mivel Magyarországon a koraszülés gyakorisága az elmúlt években nem csökkent, és a kialakult kórképek nehezen kezelhetők, a megelőzés jelentősége óriási. Kockázatifaktor-elemzések bebizonyították, hogy mindegyik kórkép multifaktoriális, a számos közös kóroki tényező közül a fejlődő szervek angiogenesise az egyik legfontosabb. A koraszülés következtében számos stresszhatás miatt károsodhat az érfejlődés. A megszületés után, a méhen belüli élethez viszonyítva, a relatív hyperoxia és a csökkenő vascularis növekedési faktorok szintje érsérü-lést, akár vascularis apoptózist okozhat. Mindezek következtében, a folyamat későbbi fázisában, a hypoxia által indukált gének aktiválódnak, óriási mértékű és kóros neovascularisatio, krónikus szervkárosodás alakul ki. A normális angiogenesis megtartása és a reaktív neovascularisatio gátlása a koraszülöttek jobb életminőségét eredményezheti. Orv. Hetil., 2013, 154, 1498-1511 Kulcsszavak: retinopathia prematurorum, bronchopulmonalis dysplasia, intraventricularis haemorrhagia, periventricularis leukomalacia Chronic morbidities of premature newbornsThe most important chronic morbidities of premature newborns, deeply infl uencing quality of life, are retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage and periventricular leukomalacia. Since the rate of premature birth has not decreased in recent years in Hungary, and treatments of these end stage disorders are extremely diffi cult, prevention gains tremendous signifi cance. Effective prevention is based on detailed knowledge of the pathophysiological mechanisms of these special diseases having multifactorial nature sharing several common risk factors, and one is the pathological angiogenesis. This sensitive system is affected by several stress situations which are the consequences of prematurity leading to abnormal vascular growth. After birth, relative hyperoxia, compared to intrauterine life, and decreasing concentrations of vascular growth factors result in vascular injury, moreover, may cause vessel apoptosis. The consequence of this phenomenon is the activation of hypoxia responsible genes resulting in robust pathological neovascularization and organ damage during the later phase. Saving normal angiogenesis and inhibiting reactive neovascularization may lead to better quality of life in these premature infants. Orv. Hetil., 2013, 154, 1498-1511 Keywords: retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia (Beérkezett: 2013. augusztus 6.; elfogadva: 2013. augusztus 22.) A szerkesztőség felkérésére készült közlemény. Rövidítések ANGPT-2 = angiopoetin-2; β-ARs = béta-adrenerg receptorok; BPD = bronchopulmonalis dysplasia; CP = cerebral palsy; ELBW = (extremely low birthweight) extrém kis születés...

show abstract

Section: Retinopathia Prematurorum (Rop)unclassified

Chronic morbidities of premature newborns

Balla

Szabó

2013

Orvosi Hetilap

View full text Add to dashboard Cite

show abstract

“…Understanding of the molecular pathogenesis of ischemic retinopathy provides the basis for identifying novel therapeutic targets. The role of the hypoxia-induced factors VEGF and erythropoietin, as well as the maternally derived factor insulin-like growth factor-1, have begun to be elucidated (for review, see Heidary et al, 2009). However, our study is the first we know of that elucidates the molecular mechanism of the tyrosine nitration of p85 leading to inactivation of the PI 3-kinase/Akt survival signal and activation of the proapoptotic p38 MAPK signal in the ischemic retinopathy model.…”

Section: Nitration Of P85 and Retinal Vaso-obliteration 131mentioning

confidence: 99%

Early Intervention of Tyrosine Nitration Prevents Vaso-Obliteration and Neovascularization in Ischemic Retinopathy

Abdelsaid

Pillai²,

Matragoon³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Diabetic retinopathy and retinopathy of prematurity are blinding disorders that follow a pathological pattern of ischemic retinopathy and affect premature infants and working-age adults. Yet, the treatment options are limited to laser photocoagulation. The goal of this study is to elucidate the molecular mechanism and examine the therapeutic effects of inhibiting tyrosine nitration on protecting early retinal vascular cell death and late neovascularization in the ischemic retinopathy model. Ischemic retinopathy was developed by exposing neonatal mice to 75% oxygen [postnatal day (p) 7-p12] followed by normoxia (21% oxygen) (p12-p17). Peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron III chloride (FeTPPS) (1 mg/kg), the nitration inhibitor epicatechin (10 mg/kg) or the thiol donor N-acetylcysteine (NAC, 150 mg/kg) were administered (p7-p12) or (p7-p17). Vascular endothelial cells were incubated at hyperoxia (40% oxygen) or normoxia (21% oxygen) for 48 h. Vascular density was determined in retinal flat mounts labeled with isolectin B4. Expression of vascular endothelial growth factor, caspase-3, and poly(ADP ribose) polymerase (PARP), activation of Akt and p38 mitogen-activated protein kinase (MAPK), and tyrosine nitration of the phosphatidylinositol (PI) 3-kinase p85 subunit were analyzed by Western blot. Hyperoxia-induced peroxynitrite caused endothelial cell apoptosis as indicated by expression of cleaved caspase-3 and PARP leading to vasoobliteration. These effects were associated with significant tyrosine nitration of the p85 subunit of PI 3-kinase, decreased Akt activation, and enhanced p38 MAPK activation. Blocking tyrosine nitration of PI 3-kinase with epicatechin or NAC restored Akt phosphorylation, and inhibited vaso-obliteration at p12 and neovascularization at p17 comparable with FeTPPS. Early inhibition of tyrosine nitration with use of epicatechin or NAC can represent safe and effective vascular-protective agents in ischemic retinopathy.Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) are potentially blinding disorders that affect premature infants and working-age adults, respectively, in the United States (Aiello et al., 1998;Chen and Smith, 2007). ROP and DR follow a pathological progression pattern characteristic of ischemic retinopathy, where the loss of retinal capillary is an early initiating event, leading to a poorly controlled process of retinal neovascularization and the development of proliferative retinopathy (for review see, Caldwell et al., 2003). So far, the standard treatment for retinal neovascularization is limited to laser photocoagulation. Although successful, this treatment is invasive and results in loss of peripheral vision (for review see, Ali and El-Remessy, 2009). The lack of approved pharmacological treatment for DR and ROP creates a great need for finding new effective therapeutic modalities to treat these devastating diseases. The mechanisms that control the process of retinal neovascularization are therefor...

show abstract

“…Third, we used a mouse model of retinopathy of prematurity (3,(31)(32)(33)(34). This model is generally accepted not only as representative of the human condition, but also as the best available model of selected features of other retinal angiogenic diseases, including diabetic retinopathy and perhaps, age-related macular degeneration (3,33).…”

Section: Resultsmentioning

confidence: 99%

From combinatorial peptide selection to drug prototype (I): Targeting the vascular endothelial growth factor receptor pathway

Giordano

Cardó-Vila

Salameh

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inhibition of blood vessel formation is a viable therapeutic approach in angiogenesis-dependent diseases. We previously used a combinatorial screening on vascular endothelial growth factor (VEGF)-activated endothelial cells to select the sequence CPQPRPLC and showed that the motif Arg-Pro-Leu targets VEGF receptor-1 and neuropilin-1. Here, we evaluated and validated D (LPR), a derivative molecule with strong antiangiogenesis attributes. This prototype drug markedly inhibits neovascularization in three mouse models: Matrigel-based assay, functional human/murine blood vessel formation, and retinopathy of prematurity. In addition to its systemic activity, D (LPR) also inhibits retinal angiogenesis when administered in an eye-drop formulation. Finally, in preliminary studies, we have showed targeted drug activity in an experimental tumor-bearing mouse model. These results show that drugs targeting extracellular domains of VEGF receptors are active, affect signal transduction, and have potential for clinical application. On a larger context, this study illustrates the power of ligand-directed selection plus retroinversion for rapid drug discovery and development.peptide | cancer | VEGFR | angiogenesis | retinopathy of prematurity

show abstract

Retinopathy of Prematurity: Current Concepts in Molecular Pathogenesis

Cited by 76 publications

References 36 publications

Chronic morbidities of premature newborns

Chronic morbidities of premature newborns

Early Intervention of Tyrosine Nitration Prevents Vaso-Obliteration and Neovascularization in Ischemic Retinopathy

From combinatorial peptide selection to drug prototype (I): Targeting the vascular endothelial growth factor receptor pathway

Contact Info

Product

Resources

About