Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.

Details

Serval ID
serval:BIB_531F1F937DD4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.
Journal
Investigative Ophthalmology and Visual Science
Author(s)
Provost A.C., Vede L., Bigot K., Keller N., Tailleux A., Jaïs J.P., Savoldelli M., Ameqrane I., Lacassagne E., Legeais J.M., Staels B., Menasche M., Mallat Z., Behar-Cohen F., Abitbol M.
ISSN
1552-5783 (Electronic)
ISSN-L
0146-0404
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
50
Number
8
Pages
3931-3942
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
PURPOSE: To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet.
METHODS: Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30 weeks. After diet supplementation, plasma cholesterol levels and electroretinograms were analyzed. Neutral lipids were detected with oil red O, and immunohistochemistry was performed on cryostat ocular tissue sections. The retina, Bruch's membrane (BM), retinal pigment epithelium (RPE), and choriocapillaris (CC) were analyzed by transmission electron microscopy.
RESULTS: Using the WT for reference, ultrastructural changes were recorded in HFC-fed SR-BI KO mice, including lipid inclusions, a patchy disorganization of the photoreceptor outer segment (POS) and the outer nuclear layer (ONL), and BM thickening with sparse sub-RPE deposits. Within the CC, there was abnormal disorganization of collagen fibers localized in ectopic sites with sparse and large vacuolization associated with infiltration of macrophages in the subretinal space, reflecting local inflammation. These lesions were associated with electroretinographic abnormalities, particularly increasing implicit time in a- and b-wave scotopic responses. Abnormal vascular endothelial growth factor (VEGF) staining was detected in the outer nuclear layer.
CONCLUSIONS: HFC-fed SR-BI KO mice thus presented sub-RPE lipid-rich deposits and functional and morphologic alterations similar to some features observed in dry AMD. The findings lend further support to the hypothesis that atherosclerosis causes retinal and subretinal damage that increases susceptibility to some forms of AMD.
Keywords
Animals, Bruch Membrane/ultrastructure, Cholates/administration & dosage, Cholesterol/blood, Choroid/blood supply, Coronary Artery Disease/etiology, Coronary Artery Disease/metabolism, Diet, Atherogenic, Electroretinography, Hypercholesterolemia/etiology, Hypercholesterolemia/metabolism, Macular Degeneration/etiology, Macular Degeneration/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Retina/physiology, Retina/ultrastructure, Retinal Pigment Epithelium/ultrastructure, Scavenger Receptors, Class B/physiology, Vascular Endothelial Growth Factor A/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
26/08/2013 14:31
Last modification date
20/08/2019 14:08
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