Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.
OBJECTIVE
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.
Université Paris-Descartes, Faculté de Médecine Paris-Descartes-site Necker, Centre de Recherche Thérapeutique en Ophtalmologie, EA 2502 CERTO, AP-HP (Assistance Publique-Hôpitaux de Paris), Paris, France.
Alexandra C
AC
Provost
Leonie
L
Vede
Karine
K
Bigot
Nicole
N
Keller
Anne
A
Tailleux
Jean-Philipe
JP
Jaïs
Michelle
M
Savoldelli
Ilhame
I
Ameqrane
Emmanuelle
E
Lacassagne
Jean-Marc
JM
Legeais
Bart
B
Staels
Maurice
M
Menasche
Ziad
Z
Mallat
Francine
F
Behar-Cohen
Marc
M
Abitbol
D000818:Animals; D016570:Bruch Membrane / Q000648:ultrastructure; D020355:Cholates / Q000008:administration & dosage; D002784:Cholesterol / Q000097:blood; D002829:Choroid / Q000098:blood supply; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004036:Diet, Atherogenic; D004596:Electroretinography; D006937:Hypercholesterolemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008268:Macular Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012160:Retina / Q000502:physiology* / Q000648:ultrastructure*; D055213:Retinal Pigment Epithelium / Q000648:ultrastructure; D051122:Scavenger Receptors, Class B / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020355:Cholates; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002784:Cholesterol