SR–BI and Apo E Interactions Affect Dark Adaptation in Mice

Abstract

Abstract: : Purpose: Apolipoprotein E (apoE) and class B type I scavenger receptor I (SR–BI) play complex roles in cholesterol transport throughout the body. SR–BI facilitates transport of cholesterol either into or out of cells in response to the concentration of extracellular and intracellular cholesterol, while apoE is a component of high density lipoproteins which mediates their hepatic clearance. ApoE deficient mice have been found by others to accumulate lipid and cholesterol–containing deposits in Bruch’s membrane similar to those present in human eyes with age–related maculopathy. The retinal phenotype of mice with mutations in SR–BI has not been described. We have sought to determine if mutations in apoE and SR–BI affect retinal structure and function in mice. Methods: Mice homozygous for null mutations in apoE (apoE –/–), heterozygous for null mutations in SR–BI (SR–BI –/+), homozygous for null mutations in apoE and heterozygous for null mutations in SR–BI (apoE –/– SR–BI –/+) and wild–type control mice were studied. Scotopic full–field electroretinograms were recorded after dark adaptation overnight. The a–wave amplitude recovery was recorded for 60 minutes after a 5–minute photobleach. Retinal and retinal pigment epithelium (RPE) structure was studied by light microscopy. Results: Scotopic a– and b–wave amplitudes were similar among the four groups. However, the mice differed significantly in rates of recovery from a photobleach (ANOVA P<0.0001). ApoE –/– mice demonstrated delayed dark adaptation compared to all other mice. SR–BI –/+ mice showed delayed dark adaptation compared to wild–type control mice. However, apoE –/– SR–BI –/+ mice demonstrated improved recovery compared to apoE –/– mice and SR–BI –/+ mice. In fact, the apoE –/– SR–BI –/+ mice demonstrated dark adaptation responses that were not significantly different from wild–type control mice (P>0.05). There were no significant differences in retinal or RPE structures at the light microscopic level. Conclusions: Mutation of SR–BI in the absence of apoE improves recovery of retinal function after exposure to a photobleach, possibly by protecting the RPE from accumulation of cholesterol from the serum.

Keywords: age-related macular degeneration • lipids • transgenics/knock-outs