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C. Savagian, R.R. Dubielzig, T.M. Nork; Distribution of Hypoxia Inducible Factor 1, Heat Shock Protein 60 and Neuroglobin in Glaucomatous and Normal Canine Retinas . Invest. Ophthalmol. Vis. Sci. 2006;47(13):409. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Identify the immunohistochemical distribution of a marker of stress [heat shock protein 60 (HSP 60)] and markers of ischemia [hypoxia inducible factor 1α (HIF–1α) and neuroglobin (Ngb)] in canine normal and glaucomatous retinas and to evaluate their role in glaucoma.
Canine globes were obtained from the Comparative Ocular Pathology Laboratory of Wisconsin. Specimens included two dogs without glaucoma and 10 dogs with glaucoma due to goniodysgenesis. Five globes had an acute (<2–day) and five globes had a chronic (>7–day) clinical history of glaucoma. The distribution of HSP 60, HIF–1α, and Ngb was determined by immunohistochemistry.
In control retinas HSP 60 stained lightly in the ganglion cell cytoplasm and the inner segments of the photoreceptor layer; the cones labeled more intensely than rods. Retinas with acute glaucoma stained more intensely than controls in the cytoplasm of ganglion cells, the outer nuclear layer and the photoreceptor layer (n=4). The rod and cone inner segments both stained intensely in 3 retinas with acute glaucoma. The synaptic cleft of photoreceptors stained positively in 1 retina. One retina with acute glaucoma was severely atrophied and did not stain with HSP 60. Retinas with chronic glaucoma were negative for HSP 60 (n=4). However, one retina with chronic glaucoma was less atrophied than its fellows, and it stained diffusely, but not more intensely, than the controls. All retinas stained positively for HIF–1α in the cytoplasm of ganglion cells and in the inner segments of the photoreceptor layer. Retinas with acute glaucoma had similar staining pattern to controls. Nuclear staining was prominent in retinas with chronic glaucoma (n=4). Nuclear staining of ganglion cells and inner nuclear layer cells was diffuse. Nuclear staining of outer nuclear layer cells was multifocal, primarily in areas of severe retinal atrophy. No definitely positive Ngb activity could be appreciated in any of the control or glaucomatous retinas.
Increased HSP 60 in acute glaucoma is consistent with its role as a chaperone protein that it is upregulated during stress. HIF–1α upregulation is likely related to retinal ischemia caused by decreased ocular blood flow, which is known to occur in glaucoma. The finding of HIF–1α labeling in all layers of the retina implies that, at various times, all parts of the retina suffer ischemic injury.
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