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C. M. Sheridan, S. Pate, P. Hiscott, D. Kent; Distribution of HIF-1-alpha and HIF-2-alpha Expression in the Human Posterior Segment. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5063.
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It is known that up regulation of pro-angiogenic cytokine expression occurring secondary to chronic hypoxia in physiologic and pathophysiologic conditions is mediated by the transcription regulators known as hypoxic inducible factors (HIF). The present study was undertaken to investigate the expression of HIF-1 alpha and HIF-2 alpha in normal human retina.
Six human globes were fixed in formalin, embedded in wax and serially sectioned for histochemical and immunohistochemical evaluation. Immunohistochemical analysis used monoclonal antibodies against markers for HIF-1 alpha and HIF-2 alpha, VEGF, cell markers CD34 (endothelial cells), wide screening cytokeratins (RPE) and CD68 (macrophages). Secondary antibody amplification was performed using Dako Envision and positive immunoreactivity was visualised with nova red substrate.
Cellular immunoreactivity for members of the HIF-1 alpha was found in none of the 6 specimens studied whilst HIF-2 alpha was found in all samples. Histological evaluation revealed the immunoreactivity to be co-localised with retinal pigment epithelial cells and not localised to the vascular or neural retina. Immunohistochemical analysis revealed areas of central retina to have an increased immunoreactivity for HIF-2 alpha in the RPE monolayer compare to cells at the periphery. No variation of VEGF staining from peripheral to central retina was observed.
Hypoxia and oxidative stress may have a role in the development of angiogenesis in AMD and the localization of HIF-2 alpha expression in RPE cells in the central region of the retina suggests that HIF-2 alpha may be involved in one or both of these mechanisms.
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