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Hypoxia-Inducible Factor 1α in the Glaucomatous Retina and OpticNerve Head

Texel G, Wax MB2004Archives of OphthalmologyJournal Article
10.1001/archopht.122.9.1348PubMed
CardiovascularEndocrine (ADH/ACTH/MSH)GastrointestinalHypothalamic-PituitaryImmune/InnateMusculoskeletalNeurologicalOcularRespiratory/Sinus
ActinomycetesBacterial EndotoxinsIndoor Mold (Stachybotrys, Aspergillus, etc.)MycotoxinsVolatile Organic Compounds (VOCs)Water-Damaged Buildings (WDB)

Abstract

OBJECTIVE: To examine tissue hypoxia in the retina and optic nerve head of glaucomatous eyes by the assessment of a transcription factor, hypoxia-inducible factor 1alpha (HIF-1alpha), which is tightly regulated by the cellular oxygen concentration. METHODS: Using immunohistochemical analysis, the cellular localization of HIF-1alpha was studied in the retina and optic nerve head of 28 human donor eyes with glaucoma compared with 20 control eyes from healthy donors matched for several characteristics. The relationship between the retinal regions that exhibited immunostaining for HIF-1alpha and functional damage was examined using visual field data. RESULTS: There was an increase in the immunostaining for HIF-1alpha in the retina and optic nerve head of glaucomatous donor eyes compared with the control eyes. In addition, the retinal location of the increased immunostaining for HIF-1alpha in some of the glaucomatous eyes was closely concordant with the location of visual field defects recorded in these eyes. CONCLUSIONS: Because the regions of HIF-1alpha induction represent the areas of decreased oxygen delivery and hypoxic stress, information obtained from this study provides direct evidence that tissue hypoxia is present in the retina and optic nerve head of glaucomatous eyes, and hypoxic signaling is a likely component of the pathogenic mechanisms of glaucomatous neurodegeneration. Clinical Relevance These findings support the presence of tissue hypoxia in the retina and optic nerve head of glaucomatous patients.

Key Biomarkers

Alpha Melanocyte Stimulating Hormone (MSH)Immunoglobulin E (IgE)LeptinMatrix Metalloproteinase 9 (MMP9)Vascular Endothelial Growth Factor (VEGF)Visual Contrast Sensitivity (VCS)

Symptom Clusters

Appetite swingsConfusionCoughDifficulty with concentrationExcessive thirstFatigueFrequent urinationHeadacheJoint painLight sensitivityMemory lossMood swingsMuscle achesNight sweatsShortness of breathSinus congestionTingling in extremitiesWord finding difficulty

Cited By (1)

  • Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanismsNeurotoxicology and Teratology · 2006

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