Distribution Of Amyloid Precursor Protein And Amyloid-Beta Immunoreactivity In Dba/2j Glaucomatous Mouse Retinas

PURPOSE. Evidence suggests that altered metabolism of amyloid precursor protein ( APP) may play a role in the pathophysiology of retinal ganglion cell ( RGC) death in the etiology of glaucoma. The authors sought to determine the distribution of APP and amyloid-beta (A beta) in DBA/2J glaucomatous mouse retinas.METHODS. The retinas of 3- and 15-month-old DBA/2J mice and C57/BL-6 mice ( control group) were fixed with 4% paraformaldehyde and processed for immunohistochemistry. Antibodies used included a polyclonal antibody to the C terminus of A beta 40 and a polyclonal antibody to the APP ectodomain. Immunohistochemically stained tissue was graded using light microscopy. Distribution and semiquantitative expression of APP and A beta in young and old glaucomatous and normal retinas were determined and compared.RESULTS. Strong APP and A beta immunoreactivity was found in the RGC layer, optic nerve, and pia/dura of old DBA/2J retinas, with considerably higher intensity found in the old compared with the young DBA/2J mice. In contrast to glaucomatous mice, the control group did not show any notable age-related difference.CONCLUSIONS. Disruption of the homeostatic properties of secreted APP with consecutive A beta cytotoxicity might be a contributing factor of ganglion cell loss in glaucomatous mouse retinas.