Distribution of Amyloid Precursor Protein and ß-Amyloid in DBA/2J Glaucomatous Mouse Retinas

Abstract

Abstract: : Purpose: Evidence suggests that altered metabolism of amyloid precursor protein (APP) plays a role in the pathophysiology of retinal ganglion cell (RGC) death in glaucoma. We determined the distribution of APP and ß-amyloid (Aß) in DBA/2J glaucomatous mouse retinas. Methods: 3 and 15 months old DBA/2J and age-matched C57/BL6 (control group) retinas were fixed with 4% paraformaldehyde and processed for immunohistochemistry using a tyramide based amplification technique and DAB as chromogen. Antibodies used included a polyclonal antibody to the C-terminus of Aß 40 (Novartis 17-40/23) and a polyclonal antibody to the APP ectodomain (Novartis 474). Immunohistochemically reactive tissue was graded (0 to 4) using light microscopy. Distribution and semiquantitative expression of APP and Aß in young and old glaucomatous and normal retinas was determined and compared. Results: The mean staining intensity of 16 eyes in each group was as follows. Conclusion: Highest APP and Aß levels were found in old glaucomatous retinas. Disruption of the homeostatic properties of secreted APP with consecutive Aß cytotoxicity might be a contributing factor of producing apoptotic cell death in mouse RGCs.  

Keywords: ganglion cells • immunohistochemistry • optic disc