title: Accelerated aging in glaucoma: immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head.
abstract: OBJECTIVE
  This study aimed to determine the association between advanced glycation end products (AGEs) and glaucoma based on the known synergism between oxidative stress with AGEs and the evidence of oxidative stress during glaucomatous neurodegeneration.
  
  
  METHODS
  The extent and cellular localization of immunolabeling for AGEs and their receptor, RAGE, were determined in histologic sections of the retina and optic nerve head obtained from 38 donor eyes with glaucoma and 30 eyes from age-matched donors without glaucoma.
  
  
  RESULTS
  The extent of AGE and RAGE immunolabeling was greater in older than in younger donor eyes. However, compared with age-matched controls, an enhanced accumulation of AGEs and an up-regulation of RAGE were detectable in the glaucomatous retina and optic nerve head. Although some retinal ganglion cells (RGCs) and glia exhibited intracellular immunolabeling for AGEs, increased AGE immunolabeling in glaucomatous eyes was predominantly extracellular and included laminar cribriform plates in the optic nerve head. Some RAGE immunolabeling was detectable on RGCs; however, increased RAGE immunolabeling in glaucomatous eyes was predominant on glial cells, primarily Müller cells.
  
  
  CONCLUSIONS
  Given that the generation of AGEs is an age-dependent event, increased AGE accumulation in glaucomatous tissues supports that an accelerated aging process accompanies neurodegeneration in glaucomatous eyes. One of the potential consequences of AGE accumulation in glaucomatous eyes appears to be its contribution to increased rigidity of the lamina cribrosa. The presence of RAGE on RGCs and glia also makes them susceptible to AGE-mediated events through receptor-mediated signaling, which may promote cell death or dysfunction during glaucomatous neurodegeneration.
authors.affiliation: Departments of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky, USA. gulgun.tezel@louiville.edu
authors.forename: Gülgün
authors.initials: G
authors.lastname: Tezel
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005902:Glaucoma, Open-Angle / Q000378:metabolism* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000378:metabolism* / Q000473:pathology; D009901:Optic Nerve Diseases / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic