Hypoxia-inducible factor 1α 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 1α (HIF-1α), which is tightly regulated by the cellular oxygen concentration. Methods: Using immunohistochemical analysis, the cellular localization of HIF-1α 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-1α and functional damage was examined using visual field data. Results: There was an increase in the immunostaining for HIF-1α 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-1α 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-1α 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.