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(Investigative Ophthalmology and Visual Science. 2007;48:5085-5090.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1249
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Distribution of Amyloid Precursor Protein and Amyloid-ß Immunoreactivity in DBA/2J Glaucomatous Mouse Retinas

David Goldblum,1,2 Anna Kipfer-Kauer,1 Gian-Marco Sarra,1 Sebastian Wolf,1 and Beatrice E. Frueh1

1From the Department of Ophthalmology, Inselspital, University of Bern, Switzerland; and the 2Department of Ophthalmology, University Hospital Basel, University of Basel, Switzerland.

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-ß (Aß) 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 Aß 40 and a polyclonal antibody to the APP ectodomain. Immunohistochemically stained tissue was graded using light microscopy. Distribution and semiquantitative expression of APP and Aß in young and old glaucomatous and normal retinas were determined and compared.

RESULTS. Strong APP and Aß 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 Aß cytotoxicity might be a contributing factor of ganglion cell loss in glaucomatous mouse retinas.






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