Objective: To examine tissue hypoxia in the retina and optic nerve head of gla ucomatous eyes by the assessment of a transcription factor, hypoxia-inducible f actor 1α(HIF-1α), which is tightly regulated by the cellular oxygen concentra tion. Methods: Using immunohistochemical analysis, the cellular localization of HIF-1αwas studied in the retina and optic nerve head of 28 human donor eyes wi th glaucoma compared with 20 control eyes from healthy donors matched for severa l characteristics. The relationship between the retinal regions that exhibited i mmunostaining for HIF-1αand functional damage was examined using visual field data. Results: There was an increase in the immunostaining for HIF-1αin the re tina and optic nerve head of glaucomatous donor eyes compared with the control e yes. In addition, the retinal location of the increased immunostaining for HIF- 1αin 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-1αinduction represent the areas of decreased oxygen delivery and hypoxic stress, information obtained from this study provides direct evidence that tissu e hypoxia is present in the retina and optic nerve head of glaucomatous eyes, an d hypoxic signaling is a likely component of the pathogenic mechanisms of glauco matous neurodegeneration. Clinical Relevance: These findings support the presenc e of tissue hypoxia in the retina and optic nerve head of glaucomatous patients.
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