ApoB100,LDLR-/- mice exhibit reduced electroretinographic response and cholesteryl esters deposits in the retina

To evaluate the retinal phenotype of 7- and 14-month-old apoB100,LDLR-/- mice, a relevant animal model of lipid metabolism dysfunction. Single-flash electroretinograms were obtained from 7- and 14-month-old apoB100,LDLR-/- and control mice fed a standard diet under both scotopic and photopic conditi...

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Published in:Investigative ophthalmology & visual science Vol. 49; no. 4; p. 1307
Main Authors: Bretillon, Lionel, Acar, Niyazi, Seeliger, Mathias W, Santos, Mylène, Maire, Marie Annick, Juanéda, Pierre, Martine, Lucy, Grégoire, Stéphane, Joffre, Corinne, Bron, Alain M, Creuzot-Garcher, Catherine
Format: Journal Article
Language:English
Published: United States 01.04.2008
Subjects:
Animals
Apolipoprotein B-100 - physiology
Basement Membrane - metabolism
Cholesterol Esters - metabolism
Dark Adaptation
Electroretinography
Female
Filipin - metabolism
Fluorescein Angiography
Lipid Metabolism Disorders - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Ophthalmoscopy
Photic Stimulation
Pigment Epithelium of Eye - metabolism
Receptors, LDL - physiology
Retina - metabolism
Retinal Diseases - metabolism
Retinal Diseases - pathology
Retinoids - metabolism
ISSN:0146-0404
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Summary:To evaluate the retinal phenotype of 7- and 14-month-old apoB100,LDLR-/- mice, a relevant animal model of lipid metabolism dysfunction. Single-flash electroretinograms were obtained from 7- and 14-month-old apoB100,LDLR-/- and control mice fed a standard diet under both scotopic and photopic conditions. Visual cycle retinoids were analyzed in eyes from dark-adapted mice. Retinal and choroidal vascularization was evaluated with scanning laser ophthalmoscopy. Fatty acids were analyzed in the retina. Esterified and free cholesterol was detected in eye cryosections. Scotopic and photopic b-wave amplitudes were significantly reduced in apoB100,LDLR-/- mice compared with control mice at 7 and 14 months of age (between -25% and -35% in 7-month-old animals and between -50% and -60% in 14-month-old animals at 25 cds/m2). Esterified cholesterol was found to accumulate at the basement of the retinal pigment epithelium in apoB100,LDLR-/- mouse eyes. On the contrary, no significant changes in the retinal profile of fatty acids and visual retinoids were observed in apoB100,LDLR-/- mice compared with control animals. The exclusive expression of apoB100 in LDL receptor-null mouse altered the ERG profile, without modifying the visual cycle of retinoids and led to cholesterol deposition in the retina. These findings clearly suggest the role of cholesterol metabolism in the functioning of the retina and possibly in the etiology of ocular diseases, including age-related macular degeneration.
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ISSN:0146-0404
DOI:10.1167/iovs.07-0808