Hypoxia in the Eye: A Two-Sided Coin

Grimm, Christian; Willmann, Gabriel

doi:10.1089/ham.2012.1031

Cited by 57 publications

(42 citation statements)

References 74 publications

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“…Retinal over-oxygenation can play an important role in ROP pathogenesis with rising ROS levels (16,17). ROS results in more oxidative damage through lipid peroxidation by invading the double bonds of polyunsaturated fatty acids.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of L-carnitine in a rat model of retinopathy of prematurity

Yıldız

Kul²,

Gökpınar³

et al. 2014

Turk J Med Sci

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Almagro et al. (2009) showed, under Mediterranean conditions, different soil CO 2 effluxes between land uses and, within uses, between beneath-and intercanopy sites. These findings have been weakly explained by soil temperature regime or soil water content, suggesting that microbial activity, as with other factors, could play a role in the soil C dynamic.Soil microbial properties are known to exhibit high space-time variability (Cavigelli et al., 2005). Understanding the spatial variability of soil properties and its functions is important in determining soil constraints to plant nutrition and appropriate management of soil resources (Keil et al., 2011).Studies carried out in natural systems showed that trees' distribution affects soil organic matter mineralization (Chatterjee and Jenerette, 2011) and soil microbial community seasonal dynamics (Waldrop et al., 2006). However, the combined effects of long-term management and trees' spatial distribution on C cycling and microbial activity have not been sufficiently investigated so far.

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Section: Discussionmentioning

confidence: 99%

Protective effect of L-carnitine in a rat model of retinopathy of prematurity

Yıldız

Kul²,

Gökpınar³

et al. 2014

Turk J Med Sci

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“…Conditions of oxygen stress cause activation of HIF1a, with increased protein levels because of both protein synthesis and stabilization of the protein. 36 As lack of WWOX mimic an oxygen stress response, we set to determine whether Wwox-deficient cells exhibit increased protein levels of HIF1a. Initially, we tested whether WWOX expression affect mRNA levels of HIF1a.…”

Section: Hif1 Target Genes Expression (Bat)mentioning

confidence: 99%

Tumor suppressor WWOX regulates glucose metabolism via HIF1α modulation

2014

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The WW domain-containing oxidoreductase (WWOX) encodes a tumor suppressor that is frequently lost in many cancer types. Wwox-deficient mice develop normally but succumb to a lethal hypoglycemia early in life. Here, we identify WWOX as a tumor suppressor with emerging role in regulation of aerobic glycolysis. WWOX controls glycolytic genes' expression through hypoxia-inducible transcription factor 1a (HIF1a) regulation. Specifically, WWOX, via its first WW domain, physically interacts with HIF1a and modulates its levels and transactivation function. Consistent with this notion, Wwox-deficient cells exhibited increased HIF1a levels and activity and displayed increased glucose uptake. Remarkably, WWOX deficiency is associated with enhanced glycolysis and diminished mitochondrial respiration, conditions resembling the 'Warburg effect'. Furthermore, Wwoxdeficient cells are more tumorigenic and display increased levels of GLUT1 in vivo. Finally, WWOX expression is inversely correlated with GLUT1 levels in breast cancer samples highlighting WWOX as a modulator of cancer metabolism. Our studies uncover an unforeseen role for the tumor-suppressor WWOX in cancer metabolism. Cell Death and Differentiation (2014) 21, 1805-1814; doi:10.1038/cdd.2014.95; published online 11 July 2014The WW domain-containing oxidoreductase (WWOX) spans one of the most active common fragile sites involved in cancer, FRA16D. WWOX encodes a 46-kDa protein that contains two N-terminal WW domains and a central shortchain dehydrogenase/reductase domain.1,2 Loss of WWOX expression has been identified in a variety of tumors (reviewed in Gardenswartz and Aqeilan 3 ). In order to understand the role of WWOX as tumor suppressor, Wwox knockout (KO) mice were generated. 4 At birth, homozygous Wwox-deficient pups were indistinguishable from wild-type (WT) or heterozygous littermates; at 3 days, homozygous pups were smaller than littermates 4 and all Wwox KO mice died by 4 weeks after birth because of severe metabolic defects, mainly hypoglycemia.5 Similar results were obtained in Wwox-conditional mouse models. 6,7 At this point, however, it remains unclear what are the basis for the molecular defects underlying this lethal hypoglycemia. Notably, juvenile Wwox KO mice and haploinsufficient heterozygous mice display higher incidence of tumor formation. 4,8,9 At the molecular level, it has been shown that WWOX, via its WW1 domain, interacts with proline-tyrosin motif-containing proteins including AP-2g, 10 ErbB4, 11 c-Jun 12 and others 13 and inhibits their transcriptional function. In a recent mass spectrometry analysis, we demonstrated that indeed the WW1 domain of WWOX provides a versatile platform that links WWOX with individual proteins associated with physiologically important networks, including metabolism.14 Recently, it has been also shown that WWOX may interact with isocitrate dehydrogenase and malate dehydrogenase in Drosophila. 15Furthermore, it has been reported that alteration in metabolism affects WWOX transcripts. 16 Critically, however, it is ...

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“…Of Note, hypoxia and HIF-1a signal pathways are crucial for the RNV during normal vascular development and pathological RNV (Fig.3) [33,34]. The development of RNV in DR is preceded by molecular and cellular changes that occur during early course of diabetes.…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Targeting neovascularization in ischemic retinopathy: recent advances

Al‐Shabrawey

El‐Sherbiny

Nussbaum

et al. 2013

Expert Review of Ophthalmology

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Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities.

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Hypoxia in the Eye: A Two-Sided Coin

Cited by 57 publications

References 74 publications

Protective effect of L-carnitine in a rat model of retinopathy of prematurity

Protective effect of L-carnitine in a rat model of retinopathy of prematurity

Tumor suppressor WWOX regulates glucose metabolism via HIF1α modulation

Targeting neovascularization in ischemic retinopathy: recent advances

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