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S. J. Fliesler, M. J. Richards, B. A. Nagel, A. K. Hennig, J. DeBrecht, P. D. Lukasiewicz; Background Modifier Gene Influence on Retinal Degenerations: The Effect of Apoe Isoform Expression on Rds Phenotype Characteristics. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6083.
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© ARVO (1962-2015); The Authors (2016-present)
Apolipoprotein E (ApoE) isoform expression has been linked to Alzheimer’s disease (AD) and age-related macular degeneration (AMD), but with paradoxically opposite trends: ApoE4 is a correlated risk factor for AD, whereas it is anti-correlated with AMD. We examined the influence of human ApoE isoform expression (APOE3 and APOE4) on retinal structure and function in rds(+/-) mice vs. wildtype (WT), APOE3/rds[+/+] and APOE4/rds[+/+] mice.
All mice were bred on a C57BL/6 background. APOE3/rds[+/+] and APOE4/rds[+/+] mice were bred with rds(-/-) mice carrying the mouse (apoE) gene to generate compound [+/-] heterozygotes. At 4 mo of age, scotopic and photopic ERGs were measured (N=4-6 per group) and the data were analyzed statistically. One retina of each was used for morphological analysis, while the other retina was used for biochemical analysis.
Retinal morphologies and ERGs of WT, APOE3/rds[+/+], and APOE4/rds[+/+] mice were all similar. Scotopic ERGs of APOE3/rds[+/-] and APOE4/rds[+/-] mice were comparable to each other; however, their a-waves (but not b-waves) were markedly depressed compared to WT, APOE3/rds[+/+], and APOE4/rds[+/+] mice. Although APOE3/rds[+/-] and APOE4/rds[+/-] retinas exhibited comparably dysmorphic features and their outer nuclear layers were ca. 40-45% thinner than in age-matched controls (as expected for the rds(+/-) phenotype), photopic ERG b-wave responses were significantly greater in APOE4/rds[+/-] vs. APOE3/rds[+/-], APOE3/rds[+/+], APOE4/rds[+/+], and WT mice. No significant differences in ERG implicit times were apparent.
Expression of human APOE isoforms per se has no negative effect on retinal structure or function in mice, nor does the E3 or E4 APOE isoform differentially protect against or promote retinal degeneration in rds(+/-) mice (as of 4 mo postnatal). However, APOE4 seems to promote or preserve healthier cone function, compared to APOE3, in rds(+/-) mice.
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