Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration

Malek, Goldis; Johnson, L.V.; Mace, Brian E.; Saloupis, Peter; Schmechel, Donald E.; Rickman, Doug; Toth, Cynthia A.; Sullivan, Patrick M.; Rickman, Catherine Bowes

doi:10.1016/j.ajo.2006.01.010

Cited by 40 publications

(58 citation statements)

References 30 publications

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“…There are basal deposits in the Timp3 S156C/S156C , mcd/mcd , ApoE4 TR, APO B100, APO*E3-Leiden, Ccl2 −/− , Ccr2 −/− , Ccl2 −/− /Cx3cr1 −/− , Efemp1 R345W/R345W , Sod2 knockdown, neprilysin −/− , mcd/mcd , CEP-immunized, and SAMP8 among other mouse models (Iwata et al, 2001; Kliffen et al, 2000; Heckenlively et al, 1995; Fogarasi et al, 2008; Zhang et al, 2002; Espinosa-Heidmann et al, 2004; Chan et al, 2008; Weber et al, 2002; Rakoczy et al, 2002; Marmorstein et al, 2007; Sandbach et al, 2001; Justilien et al, 2007; Hollyfield et al, 2008; Majji et al, 2000). Photoreceptor loss or derangement is seen in the abcr −/− , ELOVL4 -mutant, cfh −/− , Ccl2 −/− , Ccr2 −/− , Ccl2 −/− / Cx3cr1 −/− , Sod2 knockdown, mcd/mcd, Cp −/− /Heph −/Y , ApoE4 TR, arrd2/arrd2, Mfrp rd6 , Nr2e3 rd7 , and cpfl3 among other mouse models (Vasireddy et al, 2006; Weng et al, 1999; Ambati et al, 2003; Heckenlively et al, 1995; Coffey et al, 2007; Chan et al, 2008; Justilien et al, 2007; Malek et al, 2005; Chang et al, 2008; Kameya et al, 2002; Akhmedov et al, 2000; Chang et al, 2006). The Ccr2 −/− , Ccl2 −/− / Cx3cr1 −/− , ApoE(−), and APO*E3-Leiden mouse models, demonstrate the presence of dry and wet AMD features with RPE degeneration, photoreceptor loss, and CNV (Chan et al, 2008; Ambati et al, 2003; Dithmar et al, 2000; Kliffen et al, 2000).…”

Section: The Use Of Murine Models For Amdmentioning

confidence: 90%

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Ramkumar

Zhang

Chan

2010

Progress in Retinal and Eye Research

134

123

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Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch's membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD.Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr −/− (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1 R345W/R345W (Doyne honeycomb retinal dystrophy), and Timp3 S156C/S156C (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh −/− , Ccl2 −/− , Ccr2 −/− , Cx3cr1 −/− , and Ccl2 −/− /cx3cr1 −/− , oxidative stress associated genes such as Sod1 −/− and Sod2 knockdown, metabolic pathway genes such as neprilysin −/− (amyloid β), transgenic mcd/mcd (cathepsin D), Cp −/− /Heph −/Y (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically manipulated by immunization with carboxyethylpyrrole (CEP), an oxidative fragment of DHA found in drusen, and found to present with dry AMD features. Third, natural mouse strains such as arrd2/arrd2 (Mdm gene mutation) and the senescence accelerated mice (SAM) spontaneously develop features of dry AMD like photoreceptor atrophy and thickening of Bruch's membrane.Corresponding author: Chi-Chao Chan, MD, 10 Center Drive, 10/10N103, NIH/NEI, Bethesda, MD 20892-1857. Tel: (301), 496-0417, Fax: (301) 402-8664, chanc@nei.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public AccessAuthor Manuscript Prog Retin Eye Res. Author ma...

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Section: The Use Of Murine Models For Amdmentioning

confidence: 90%

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Ramkumar

Zhang

Chan

2010

Progress in Retinal and Eye Research

134

123

View full text Add to dashboard Cite

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“…To date, different types of research have tried to create such a new model. Knock-out or transgenic mice with alteration of apoE, a component of lipoproteins, or cathepsin D, predominant lysosomal enzyme of RPE cells, exhibited deposits similar to BlinD or BlamD, which suggested that basal deposits might result from impaired metabolism or transport system of the RPE cells [43][44][45][46]. Another BlamD model was induced by a high-fat diet and laser photochemical injury of Bruch's membrane in mice, which suggested that hyperlipidemia also might be related to aging changes in Bruch's membrane involving its thickening and BlamD [47].…”

Section: Discussionmentioning

confidence: 99%

Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits

Yasukawa

Wiedemann

Hoffmann

et al. 2007

Graefes Arch Clin Exp Ophthalmol

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“…However, Malek et al recently showed that older mice expressing human apoE2, E3, or E4 isoforms and consuming a high fat diet accumulate oil red O binding material in the sub-RPE space. 65 Determining the source of this material in future animal models permitting independent manipulation of RPE and plasma derived lipoproteins will be of great interest.…”

Section: Discussionmentioning

confidence: 99%

Plasma apolipoproteins and risk for age related maculopathy

Dashti

McGwin²,

Owsley³

et al. 2006

British Journal of Ophthalmology

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Although drusen associated with ARM and ageing contain cholesterol and apoB, like the lipid rich core of an atherosclerotic plaque, the results of this study and our previous work in toto make the prospects of a plasma origin for these lesion constituents increasingly untenable. This conclusion is consistent with an emerging hypothesis that a large lipoprotein of intraocular origin is an important pathway for constituent retinal lipid processing and the biogenesis of drusen.

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Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration

Cited by 40 publications

References 30 publications

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)

Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits

Plasma apolipoproteins and risk for age related maculopathy

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