The APO*E3-Leiden mouse as an animal model for basal laminar deposit

Aim-To investigate the APO star E3-Leiden mouse as an animal model for age related maculopathy (ARM) related extracellular deposits. Methods-Eyes were obtained from APO star E3-Leiden transgenic mice on a hig h fat/cholesterol (HFC) diet (n=12) or on a normal mouse chow (n=6), for 9 months. As controls, eyes were collected from APO-E knockout mice on the sa me diets. From each mouse one eye was processed for microscopic evaluation and immunohistochemistry with a polyclonal antibody directed against human apo-E. Electron microscopy was also performed. Results-All 12 eyes of the APO star E3-Leiden mice on an HFC diet contained basal laminar deposit (BLD; class 1 to class 3), whereas two of six APO st ar E3-Leiden mice on normal chow showed BLD class 1. The ultrastructural as pects of this BLD were comparable with those seen in early BLD in humans, a nd BLD showed immunoreaction with anti-human-apo-E antibodies. No BLD was f ound in any of the control mice. Drusen were not detected in any of the mic e. Conclusion-These results indicate that APO star E3-Leiden mice can be used as animal model for the pathogenesis of BLD, and that a HFC diet enhances t he accumulation of this deposit. Furthermore, this study supports the previ ously suggested involvement of dysfunctional apo-E in the accumulation of e xtracellular deposits in ARM.