AIM: To investigate the APO(*)E3-Leiden mouse as an animal model for age related maculopathy (ARM) related extracellular deposits. METHODS: Eyes were obtained from APO(*)E3-Leiden transgenic mice on a high 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 same 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(*)E3-Leiden mice on an HFC diet contained basal laminar deposit (BLD; class 1 to class 3), whereas two of six APO(*)E3-Leiden mice on normal chow showed BLD class 1. The ultrastructural aspects of this BLD were comparable with those seen in early BLD in humans, and BLD showed immunoreaction with anti-human-apo-E antibodies. No BLD was found in any of the control mice. Drusen were not detected in any of the mice. CONCLUSION: These results indicate that APO(*)E3-Leiden mice can be used as animal model for the pathogenesis of BLD, and that a HFC diet enhances the accumulation of this deposit. Furthermore, this study supports the previously suggested involvement of dysfunctional apo-E in the accumulation of extracellular deposits in ARM.
AIM: To investigate the APO(*)E3-Leiden mouse as an animal model for age related maculopathy (ARM) related extracellular deposits. METHODS: Eyes were obtained from APO(*)E3-Leiden transgenic mice on a high 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 same diets. From each mouse one eye was processed for microscopic evaluation and immunohistochemistry with a polyclonal antibody directed against humanapo-E. Electron microscopy was also performed. RESULTS: All 12 eyes of the APO(*)E3-Leiden mice on an HFC diet contained basal laminar deposit (BLD; class 1 to class 3), whereas two of six APO(*)E3-Leiden mice on normal chow showed BLD class 1. The ultrastructural aspects of this BLD were comparable with those seen in early BLD in humans, and BLD showed immunoreaction with anti-human-apo-E antibodies. No BLD was found in any of the control mice. Drusen were not detected in any of the mice. CONCLUSION: These results indicate that APO(*)E3-Leiden mice can be used as animal model for the pathogenesis of BLD, and that a HFC diet enhances the accumulation of this deposit. Furthermore, this study supports the previously suggested involvement of dysfunctional apo-E in the accumulation of extracellular deposits in ARM.
Authors: J K Boyles; C D Zoellner; L J Anderson; L M Kosik; R E Pitas; K H Weisgraber; D Y Hui; R W Mahley; P J Gebicke-Haerter; M J Ignatius Journal: J Clin Invest Date: 1989-03 Impact factor: 14.808
Authors: Lan Wang; Chuan-Ming Li; Martin Rudolf; Olga V Belyaeva; Byung Hong Chung; Jeffrey D Messinger; Natalia Y Kedishvili; Christine A Curcio Journal: Invest Ophthalmol Vis Sci Date: 2008-09-20 Impact factor: 4.799
Authors: Christine M Bojanowski; Defen Shen; Emily Y Chew; Baitang Ning; Karl G Csaky; W Richard Green; Chi-Chao Chan; Jingsheng Tuo Journal: Environ Mol Mutagen Date: 2006-10 Impact factor: 3.216
Authors: G Malek; L V Johnson; B E Mace; P Saloupis; D E Schmechel; D W Rickman; C A Toth; P M Sullivan; C Bowes Rickman Journal: Proc Natl Acad Sci U S A Date: 2005-08-03 Impact factor: 11.205