Purpose : Changes in the proteolytic enzymes and proteasomal proteins has been associated with Alzheimer’s disease (AD) pathology in the brains. This dysregulation in proteolytic machinery may impair the ability of brain to clear amyloid beta and other misfolded proteins in disease conditions. The effects of AD pathology on the proteolytic and proteasomal enzyme expression changes in retina might provide insights into the molecular effects of AD on the eyes. Here, we examined proteolytic and proteasomal enzyme expression changes in the retinas of an APP/PS1 mouse model of AD.
Methods : WT and APP/PS1 (8 month) mice retinas were examined using mass spectrometry (MS) and data obtained was subjected to in-depth computational analysis using STRING and PANTHER tools. The retinal biochemical changes were further evaluated using western blotting and immunofluorescence analysis of the retinal sections (n=10).
Results : MS data revealed significantly increase levels of proteolytic enzymes and proteasomal proteins in the retinas of AD (p<0.05) mouse model compared to age matched wild type animals (approx 2000 proteins identified in each set, upregulated proteins 85; downregulated 79). Immunofluorescence (n=3) analysis of retinal sections in AD mice demonstrated significantly increased Cathapsin D, presenlin 2 and Nicastrin proteins compared to the WT counterparts. IF staining further revealed increased expression levels of Psma5, Psmd3 and Psmb2 proteasomal proteinsin the retinas in AD pathology.
Conclusions : This study provides evidence for activation of proteolytic enzymes in eight month old APP/PS1 mice. This may represent may represent a cellular response in retina against AD, potentially to clear amyloid build-up. Further studies will examine the potential effects of modulating these enzymes in the retina, which in turn could help design new treatment strategies to preserve or regenerate neurons.