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T.W. Lauer, S.F. Hackett, R. Formica, K. Yokoi, N.H. Khu, S. Henry, P.A. Campochiaro; Inhibition of Laser–Induced Choroidal Neovascularization in Mice Using Antisense Oligonucleotides Directed Against HIF–1 or HIF–1ß . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1428.
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Antisense oligonucleotides provide a useful way to explore the role of particular genes in disease pathogenesis. Hypoxia–inducible factor (HIF) is a heterodimeric transcription factor, with HIF–1α and HIF–1ß subunits, that regulates expression of many proangiogenic factors. In this study, we used antisense oligonucleotides generated against the mRNAs of HIF–1α and HIF–1ß to investigate the role of each subunit in the development of choroidal neovascularization (CNV) after rupture of Bruch's membrane.
Immediately after laser disruption of Bruch’s membrane, mice were given a 1 µl intravitreous injection of scrambled control oligo, anti–HIF–1α oligo, anti–HIF–1ß oligo, or saline. After 14 days, mice were perfused with fluorescein–labeled dextran and the area of CNV at rupture sites was measured on choroidal flat mounts.
In paired comparisons, both anti–HIF–1α and anti–HIF–1ß oligos significantly inhibited the development of CNV compared to the control oligo or saline. Compared to injection of saline, injection of 14 µg of the anti–HIF–1α or anti–HIF–1ß oligo decreased the mean area of CNV by 55.0% or 32.3%, respectively. Injection of 1 µg of the anti–HIF–1ß oligo decreased the mean area of CNV by 60.0% compared to injection of 1 µg of control oligo. Comparison of saline and control oligo groups showed no significant difference in CNV area.
These data indicate that both HIF–1α and HIF–1ß play a role in the development of CNV at Bruch's membrane rupture sites and provide potential targets for therapeutic intervention.
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