Impaired electroretinogram (ERG) response in apolipoprotein E-deficient mice.
OBJECTIVE
We investigated the effects of 35 weeks of a cholesterol diet in apolipoprotein E (apoE)-deficient mice on their ERG response.


METHODS
C57BL/6J and apoE-deficient mice were fed regular mouse chow (C57-R and ApoE-R, respectively) or a cholesterol-containing diet (C57-C and ApoE-C, respectively). Retinal function was assessed by dark-adapted electroretinography (ERG). Retina tissue was also analyzed by immunohistochemical staining and nucleic acid array expression analysis performed by gene array technology.


RESULTS
ApoE-C mice had diminished a- and b-wave amplitudes (60.7% +/- 8.4% (p < 0.005) and 44.8% +/- 10% (p < 0.005) of control values, respectively). Gene expression profiling revealed upregulation of several pro-apoptotic genes. Furthermore, immunohistochemistry showed increased Bax immunoreactivity.


CONCLUSIONS
In the hypercholesterolemic mice, we demonstrated a loss of ERG response and induction of apoptotic activity at the gene and protein levels. Our current and previous findings suggest that cholesterol metabolism plays an important role in retinal function.
Ong
John M
JM
Molecular Eye Research Laboratory, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ongj@cshs.org
Zorapapel
Nadia C
NC
Aoki
Annette M
AM
Brown
Donald J
DJ
Nesburn
Anthony B
AB
Rich
Kathryn A
KA
Kenney
Cristina M
CM
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D017209:Apoptosis / Q000235:genetics; D064032:Calbindin 2; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004596:Electroretinography; D015870:Gene Expression; D020869:Gene Expression Profiling; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
D001057:Apolipoproteins E; C494827:Bax protein, mouse; D064032:Calbindin 2; D002791:Cholesterol, Dietary; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D064030:S100 Calcium Binding Protein G; D051028:bcl-2-Associated X Protein