Active HIF-1 in the Normal Human Retina

Hughes, John M.; Groot, Arjan J.; Groep, Petra van der; Sersansie, R.; Vooijs, Marc; Diest, Paul J. van; Noorden, C. J. F. Van; Schlingemann, Reinier O.; Klaassen, Ingeborg

doi:10.1369/jhc.2009.953786

Cited by 42 publications

(33 citation statements)

References 41 publications

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“…Hughes et al . have earlier reported the presence of stabilized HIF‐1α in normal physiological human and rat retinas . The presence of PKM2 in mouse retina was demonstrated by Morohoshi et al .…”

Section: Mammalian Retinal Metabolismmentioning

confidence: 80%

Cancer‐like metabolism of the mammalian retina

Wood

Chidlow

et al. 2014

Clinical Exper Ophthalmology

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The retina, like many cancers, produces energy from glycolysis even in the presence of oxygen. This phenomenon is known as aerobic glycolysis and eponymously as the Warburg effect. In recent years, the Warburg effect has become an explosive area of study within the cancer research community. The expanding knowledge about the molecular mechanisms underpinning the Warburg effect in cancer promises to provide a greater understanding of mammalian retinal metabolism and has motivated cancer researchers to target the Warburg effect as a novel treatment strategy for cancer. However, if the molecular mechanisms underlying the Warburg effect are shared by the retina and cancer, treatments targeting the Warburg effect may have serious adverse effects on retinal metabolism. Herein, we provide an updated understanding of the Warburg effect in mammalian retina.

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Section: Mammalian Retinal Metabolismmentioning

confidence: 80%

Cancer‐like metabolism of the mammalian retina

Wood

Chidlow

et al. 2014

Clinical Exper Ophthalmology

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“…HIF‐1α is abundantly expressed in the retina (46). Dozens of target genes of HIF‐1α have been identified.…”

Section: Discussionmentioning

confidence: 99%

HIF‐1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa

et al. 2018

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Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 ( retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice. A generalized down-regulation of HIF-1α and its downstream targets was detected in parallel with reactive gliosis, suggesting high oxygen levels during retinal degeneration. At postnatal d 18, DMOG treatment reduced photoreceptor cell death and glial activation. In summary, retinas of rd10 mice seem to be exposed to a hyperoxic environment even at early stages of degeneration. HIF-1α stabilization could have a temporal neuroprotective effect on photoreceptor cell survival, glial activation, and antioxidant response at early stages of RP.-Olivares-González, L., Martínez-Fernández de la Cámara, C., Hervás, D., Millán, J. M., Rodrigo, R. HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

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“…Conversely, expression of HIF-1α is unique in that its accumulation could theoretically increase immediately after tissue hypoxia associated with circulatory arrest. In a recent study looking at basal HIF-1α and VEGF levels in normal human retina, a modest negative correlation has been found between the expression of HIF-1α and postmortem times, 26 suggesting that HIF-1α behaves similarly to other proteins in human eyes. For our studies, we used autopsy specimens that were acquired (enucleated) within 5 hours of death.…”

Section: Discussionmentioning

confidence: 99%

Expression Pattern of HIF-1α and VEGF Supports Circumferential Application of Scatter Laser for Proliferative Sickle Retinopathy

Rodrigues

Kashiwabuchi

Deshpande

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeRetinal vascular occlusions in sickle cell anemia patients cause tissue ischemia and the release of angiogenic mediators that promote the development of retinal neovascularization, initiating proliferative sickle retinopathy (PSR). Laser photocoagulation (LPC) has emerged as the most common treatment for PSR. Nonetheless, only two randomized controlled clinical trials have evaluated the use of LPC for PSR, and both failed to definitively demonstrate efficacy of this approach. This may be due to a lack of knowledge regarding the appropriate location for placement of laser coagulations in PSR eyes. To help address this question, we examined the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in PSR eyes.MethodsThe expression pattern of HIF-1α and VEGF in PSR (n = 5) and control (n = 3) eyes was examined by immunohistochemistry in different retinal regions defined by the presence or absence of retinal vessels.ResultsHypoxia-inducible factor 1α and VEGF were expressed in the inner retina of 5/5 untreated PSR eyes adjacent to retinal neovascularization; expression of HIF-1α was not detected (and VEGF only lightly detected) in normal retinal and choroidal vasculature of 3/3 control eyes. Hypoxia-inducible factor 1α and VEGF were strongly expressed in retinal cells within avascular (nonperfused) retina, anterior to the boundary between perfused and nonperfused retina, as well as in posterior ischemic retina in the presence or absence of neovascular sea fans.ConclusionsIf the goal of LPC in PSR is to quench the expression of HIF-1–driven angiogenic mediators, our results support broad application of peripheral laser for its treatment.

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Active HIF-1 in the Normal Human Retina

Cited by 42 publications

References 41 publications

Cancer‐like metabolism of the mammalian retina

Cancer‐like metabolism of the mammalian retina

HIF‐1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa

Expression Pattern of HIF-1α and VEGF Supports Circumferential Application of Scatter Laser for Proliferative Sickle Retinopathy

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