Distribution of amyloid precursor protein and amyloid-beta immunoreactivity in DBA/2J glaucomatous mouse retinas.
OBJECTIVE
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 (Abeta) 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 Abeta 40 and a polyclonal antibody to the APP ectodomain. Immunohistochemically stained tissue was graded using light microscopy. Distribution and semiquantitative expression of APP and Abeta in young and old glaucomatous and normal retinas were determined and compared.


RESULTS
Strong APP and Abeta 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 Abeta cytotoxicity might be a contributing factor of ganglion cell loss in glaucomatous mouse retinas.
Goldblum
David
D
Department of Ophthalmology, Inselspital, University of Bern, Switzerland. dgoldblum@uhbs.ch
Kipfer-Kauer
Anna
A
Sarra
Gian-Marco
GM
Wolf
Sebastian
S
Frueh
Beatrice E
BE
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004388:Dura Mater / Q000378:metabolism; D005260:Female; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009900:Optic Nerve / Q000378:metabolism; D010841:Pia Mater / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor