June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Transcriptome Analysis Indicates Hypoxia-Inducible Factor-1alpha as a Key Regulator of Choroidal Neovascularization
Author Affiliations & Notes
  • Helder Andre
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Stockholm, Sweden
    Sankt Eriks Ogonsjukhus, Solna, Sweden
  • Alexander Handyside
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Stockholm, Sweden
  • Jonathan Bernd
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Stockholm, Sweden
    Sankt Eriks Ogonsjukhus, Solna, Sweden
  • Flavia Plastino
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Stockholm, Sweden
  • Anders Kvanta
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Stockholm, Sweden
    Sankt Eriks Ogonsjukhus, Solna, Sweden
  • Footnotes
    Commercial Relationships   Helder Andre None; Alexander Handyside None; Jonathan Bernd None; Flavia Plastino None; Anders Kvanta None
  • Footnotes
    Support  KI foundations
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2316. doi:
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      Helder Andre, Alexander Handyside, Jonathan Bernd, Flavia Plastino, Anders Kvanta; Transcriptome Analysis Indicates Hypoxia-Inducible Factor-1alpha as a Key Regulator of Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2316.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The aim of this study was to determine the role the hypoxia-inducible factor-1alpha (HIF-1α) plays in the development of the neovascular form of age-related macular degeneration (nAMD).

Methods : Choroidal neovascularization (CNV) was laser-induced in C57Bl/6J mice, a model that leads to relative hypoxia in the outer retinal layers and upregulation of HIF-1α expression in the retinal pigment epithelium (RPE) cells, thus simulating nAMD. The mice were then euthanized during the peak of hypoxia (day 9) or after recovery from CNV (day 30), and compared to non-induced mice (day 0). Total RNA was purified from isolated RPE/choroid/sclera complexes with data collected through quantitative PCR and analysis completed using the program R.

Results : Expectedly, the regulation at the transcript level was insignificant, yet HIF-1α became activated through genetic upregulation of several target genes. Analysis showed upregulation of a number of angiogenic genes, including vascular endothelial growth factor and fibroblast growth factor 2, during the peak of hypoxia with a resolution to baseline of these same genes once CNV and hypoxia had resolved. Moreover, HIF-1α mediated the upregulation of a series of nAMD-associated inflammatory genes, particularly tumor necrosis factor and interleukin-1b and -6, with resolution after CNV.

Conclusions : Our data demonstrates the role of HIF-1α in mediating the upregulation of both angiogenic and inflammatory factors associated with nAMD. Our findings indicate that HIF-1α is a key regulatory molecule in the progression of nAMD and would be an ideal target in future treatments of the disease.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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