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Hypoxia-Inducible Factor (HIF)/Vascular Endothelial Growth Factor (VEGF) Signaling in the Retina

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Over a span of two decades, it has become increasingly clear that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR). Based on these observations, anti-VEGF therapies are being developed and approved for clinical use in the treatment of neovascular eye diseases. Hypoxia-inducible factors (HIFs) are transcriptional factors that are stabilized and activated under hypoxic conditions and induce expression of gene products, including VEGF, that are required for cell survival under hypoxia. Here we discuss recent findings from our lab and others that define roles of the HIF-VEGF axis in the retina.

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Abbreviations

VEGF:

Vascular endothelial growth factor

AMD:

Age-related macular degeneration

DR:

Diabetic retinopathy

HIFs:

Hypoxia-inducible factors

ARNTs:

Aryl hydrocarbon receptor nuclear translocators

PHDs:

HIF prolyl hydroxylases

NOSs:

Nitric oxide synthases

GLUTs:

Glucose transporters

VHL:

Von Hippel-Lindau disease gene

RPE:

Retinal pigment epithelium

PHPV:

Persistent hypertrophic primary vitreous

OIR:

Oxygen-induced retinopathy

ROP:

Retinopathy of prematurity

CNV:

Choroidal neovascularization

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Acknowledgments

We wish to warmly thank all members of the Friedlander lab and our collaborators. Work discussed in this chapter was supported by fellowships to TK (Manpei Suzuki Diabetes Foundation and The Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad) and to PDW (a Ruth Kirschstein Fellow NEI EY021416). MF gratefully acknowledges the generous support of the research in our lab from the National Eye Institute of the National Institutes of Health (EY11254 and EY017540), the California Institute for Regenerative Medicine (CIRM TR1–01219), the Lowy Medical Research Foundation (the MacTel Project), and the Rasmussen Foundation.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd. La Jolla, 92014, San Diego, CA, USA

    Toshihide Kurihara, Peter D. Westenskow & Martin Friedlander MD PhD

Authors
  1. Toshihide Kurihara
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  2. Peter D. Westenskow
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  3. Martin Friedlander MD PhD
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Corresponding author

Correspondence to Martin Friedlander MD PhD .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Kurihara, T., Westenskow, P., Friedlander, M. (2014). Hypoxia-Inducible Factor (HIF)/Vascular Endothelial Growth Factor (VEGF) Signaling in the Retina. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_35

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_35

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