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. 2000 Dec;84(12):1415–1419. doi: 10.1136/bjo.84.12.1415

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

M Kliffen 1, E Lutgens 1, M Daemen 1, E D de Muinck 1, C Mooy 1, P T V M de Jong 1
PMCID: PMC1723360  PMID: 11090485

Abstract

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.



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Figure 1  .

Figure 1  

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Light microscopic images of (A) a continuous layer (class 2) of basal laminar deposit (arrow), between the retinal pigment epithelium (R) and Bruch's membrane, in the central retina of an APO*E3-Leiden mouse on a high fat/cholesterol (HFC) diet. (B) the central retina from an APO*E3-Leiden mouse on normal chow, without basal laminar deposit (BLD class 0). Note the thin Bruch's membrane between the RPE (R) and the choroidal melanin (M). (C, D) The central retinas of APO-E knockout mice (without BLD) on a (C) normal, and (D) HFC diet, respectively. (E, F) a continuous layer (class 2) of basal laminar deposit, between the RPE and Bruch's membrane, in the central retina of an APO*E3-Leiden mouse on an HFC diet. (E) Stained with an anti-human apo-e antibody (BLD stains red). (F) Negative control. Scale bar indicates 10 µm.

Figure 2  .

Figure 2  

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Electron micrograph of basal laminar deposit (BLD) class 2, between the cell membrane of the retinal pigment epithelium (RPE) and the basement membrane of the RPE, in a central retina from an APO*E3-Leiden mouse on a high fat/cholesterol diet. Furthermore, there is an increase and elongation of the basal infoldings of the RPE (*). Uranyl acetate/lead citrate staining. Scale bar indicates 1.1 µm. N = nucleus of RPE; C = choriocapillaris.

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