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Abstract #27315 Published in IGR 12-4
Hypoxia inducible factor-1(alpha) (HIF-1(alpha)) and some HIF-1 target genes are elevated in experimental glaucoma
Ergorul C; Ray A; Huang W; Wang DY; Ben Y; Cantuti-Castelvetri I; Grosskreutz CLJournal of Molecular Neuroscience 2010; 42: 183-191
Low levels of hypoxia have been suggested to be a mechanism of retinal damage in glaucoma. To test the hypothesis that the activation of the hypoxia-responsive transcription factor hypoxia inducible factor-1(alpha) (HIF-1(alpha)) is involved in the pathophysiology of glaucoma, we used a rat model of glaucoma to study (1) HIF-1(alpha) retinal protein levels by immunoblot analysis, (2) cellular localization of HIF-1(alpha) in the retina by immunohistochemistry, and (3) expression of retinal HIF-1 gene targets by quantitative real-time polymerase chain reaction. Glaucoma was unilaterally induced in rats by injecting hypertonic saline in episcleral veins. We find that HIF-1(alpha) protein was increased in the retina following elevation of intraocular pressure, specifically in Muller glia and astrocytes but not in activated microglia. Eight established HIF-1 target genes were measured in experimental glaucoma. Retinal Epo, Flt-1, Hsp-27, Pai-1, and Vegfa mRNA levels were increased and Et-1, Igf2, and Tgf(beta)3 levels were decreased in the glaucomatous retinas. Thus, the increase in HIF-1(alpha) levels in Muller glia and astrocytes is accompanied by a marked up regulation of some, but not all, HIF-1 transcriptional targets. These data support the hypothesis that HIF-1(alpha) becomes transcriptionally active in astrocytes and Muller cells but not microglia or neurons in glaucoma, arguing against a global hypoxia stimulus to the retina. (copyright) 2010 Springer Science+Business Media, LLC.
C. L. Grosskreutz. Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA 02114, United States. cynthia_grosskreutz@meei.harvard.edu
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
