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C. Luo, X. Yang, G. Tezel; Accelerated Aging in Glaucoma: Immunohistochemical Assessment of Advanced Glycation End–Products in the Human Retina and Optic Nerve Head . Invest. Ophthalmol. Vis. Sci. 2006;47(13):398.
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Due to their known synergism with oxidative stress, advanced glycation end products (AGEs) have been implicated in many neurodegenerative diseases. Based on the growing evidence demonstrating the involvement of oxidative damage in glaucomatous neurodegeneration, this study aimed to determine the association of AGEs and their receptor with glaucoma through an immunohistochemical analysis of human eyes.
The extent and cellular localization of immunolabeling for AGEs and receptor for AGE (RAGE) were determined in histological sections of the retina and optic nerve head obtained from 34 donor eyes with a diagnosis of glaucoma and 20 eyes from age–matched donors without glaucoma. Immunoperoxidase staining and double immunofluorescence labeling with specific antibodies were qualitatively and quantitatively graded in a masked fashion.
The extent of retinal AGE and RAGE immunolabeling was relatively greater in older compared with younger donor eyes. However, in comparison to age–matched controls, an advanced accumulation of AGEs and up–regulation of RAGE were detectable in the glaucomatous retina and optic nerve head. The extent of AGE immunolabeling was 33+4% and 36+5% in the glaucomatous retina and optic nerve head, respectively, but less than 8% in the age–matched controls. Although some RGCs and glia exhibited granular intracellular immunolabeling for AGEs, the increased AGE immunolabeling in glaucomatous eyes was predominantly extracellular, which included laminar cribriform plates in the optic nerve head. The extent of RAGE immunolabeling was 14+2% and 9+1% in the glaucomatous retina and optic nerve head, respectively, but less than 3% in the age–matched controls. Some RAGE immunolabeling was detectable on scattered RGCs; however, the increased RAGE immunolabeling in glaucomatous eyes was predominant on glial cells, mainly including Müller cells in the retina.
Since the generation of AGEs is an age–dependent event, these findings support that an accelerated aging process accompanies neurodegeneration in glaucomatous eyes. Among several consequences of AGE accumulation in glaucomatous eyes, one may be its contribution to increased rigidity of the lamina cribrosa in the glaucomatous optic nerve head. Presence of RAGE on RGCs and glia also makes them susceptible for AGE–mediated events through receptor–mediated signaling which may promote cell death and/or dysfunction in glaucoma.
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