Hypoxia-inducible factor 1alpha in the glaucomatous retina and optic nerve head.
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.
Tezel
Gülgün
G
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA. gulgun.tezel@louisville.edu
Wax
Martin B
MB
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005902:Glaucoma, Open-Angle / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007124:Immunoenzyme Techniques; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014792:Visual Acuity; D014794:Visual Fields
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors