Optic Nerve Alterations in Apolipoprotein E Deficient Mice

Abstract

Purpose

To study the morphologic characteristics of the optic nerve (ON) by using an experimental model of knockout mice for expression of the ApoE gene

Methods

Eyeballs with the retrobulbar ON attached were obtained from 24-week-old mice. Using morphologic and morphometric techniques and light and transmission electron microscopy, the ON characteristics were determined in three groups of mice: 1) wild type mice as the controls (CG; n=15), 2) knockout mice for the ApoE gene (ApoE-G; n=15), and 3) knockout mice for the ApoE gene that were fed a cholesterol-supplemented diet (ApoED-G; n=15).

Results

The ON cross-sectional area was significantly higher in the ApoE-G than in the CG (p<0.001) mice, whereas no significant changes were noticed between the ApoE-G and ApoED-G mice. Significant differences were noticed between those groups regarding the myelination index. Higher density of intraaxonal degeneration and myelin sheath alterations were found in both ApoE groups in respect to the CG.

Conclusions

These results suggest that ApoE knockout mice have changes in ON morphology and myelination.

Keywords

Apolipoprotein E Knockout Optic nerve Morphology Morphometry.

Get full access to this article

View all access options for this article.

References

Knouff

Heinsdale

M.E.

Mezdour

ApoE structure determines VLDL clearance and atherosclerosis risk in mice.

J Clin Invest 1999; 103: 1579–85.

Zhang

S.H.

Reddick

R.L.

Burkey

Maeda

. Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption. J Clin Invest 1994; 94: 937–45.

Fullerton

S.M.

Strittmatter

W.J.

Matthew

W.D.

. Peripheral sensory nerve defects in apolipoprotein E knockout mice. Exp Neurol 1998; 153: 156–63.

Moghadasian

M.H.

McManus

B.M.

Nguyen

L.B.

Pathophysiology of apolipoprotein E deficiency in mice: relevance to apoE-related disorders in humans.

FASEB J 2001; 14: 2623–30.

Shanmugaratnam

Berg

Kimerer

Retinal Müller glia secrete apolipoproteins E and J which are efficiently assembled into lipoprotein particles.

Brain Res Mol Brain Res 1997; 50: 113–20.

Amaratunga

Abraham

C.R.

Edwards

R.B.

Sandell

J.H.

Schreiber

B.M.

. Apolipoprotein E is synthesized in the retina by Muller glial cells, secreted into vitreous, and rapidly transported into the optic nerve by retinal ganglion cells. J Biol Chem 1996; 271: 5628–32.

Ong

J.M.

Zorapapel

N.C.

Rich

K.A.

Effects of cholesterol and apolipoprotein E on retinal abnormalities in apoE-deficient mice.

Invest Ophthalmol Vis Sci 2001; 42: 1891–900.

Dithmar

Curcio

C.A.

Brown

Grossniklaus

H.E.

. Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice. Invest Ophthalmol Vis Sci 2000; 41: 2035–42.

Anderson

D.H.

Ozaki

Nealson

Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications in the process of drusen formation.

Am J Ophthalmol 2001; 131: 767–81.

10.

Klaver

Kliffen

Van Duijn

C.M.

Genetic association of apolipoprotein E with age-related macular degeneration.

Am J Hum Genet 1998; 63: 200–6.

11.

Souied

E.H.

Benlian

Amouyel

The epsilon 4 allele of the apolipoprotein E gene as potential protective factor for exudative age-related macular degeneration.

Am J Ophthalmol 1998; 125: 353–9.

12.

Schmidt

Saunders

A.M.

De la Paz

Association of the apolipoprotein E gene with age-related macular degeneration: possible effect modifications by family history, age and gender.

Mol Vis 2000; 6: 287–93.

13.

Copin

Brazin

A.P.

Valtot

Dascotte

J.C.

Bachetoille

Garchon

H.J.

. Apolipoprotein E-promoter single-nucleotide polymorphism affected the phenotype of primary open-angle glaucoma and demonstrate interaction with the myocilin gene. Am J Hum Genet 2002; 70: 1575–81.

14.

Kuhrt

Horti Grimm

Faude

Kasper

. Reichenbach changes in CD44 and apoE immunoreactivities due to retinal pathology of man and rat. J Hirnforsch 1997; 38: 223–9.

15.

Matius

M.J.

Gebicke

Skene

Schillin Weisgraber

K.H.

Shooter

E.M.

. Expression of apolipoprotein E during nerve degeneration and regeneration. Proc Natl Acad Sci 1986; 3: 1125–9.

16.

Stoll

Mueller

H.W.

Trapp

B.D.

Griffin

J.W.

. Oligodendrocytes but not astrocytes express apolipoprotein E after injury of rat optic nerve. Glia 1989; 2: 170–6.

17.

Kosco-Vilbois

M.H.

. IL-18. A destabilizer of atherosclerotic disease. Trends Immunol 2002; 23: 123.

18.

Bonthus

Heistad

D.D.

Chappell

D.A.

Lamping

K.G.

Fraci

F.M.

. Atherosclerosis, vascular remodelling, and impairment of endothelium-dependent relaxation in genetically altered hyperlipidemic mice. Arterioscler Thromb Biol 1997; 17: 2333–40.

19.

Laskowitz

D.T.

Sheng

Bart

Joyner

Roses

A.D.

Warner

. Apolipoprotein E deficient mice have increased susceptibility to focal cerebral ischemia. J Cereb Blood Flow Metab 1997; 17: 753–8.

20.

Carling

Muray

Graham

Doyle

Nicoll

. Involvement of apolipoprotein E in multiple sclerosis: absence of remyelination associated with possession of the apoE epsilon 2 allele. J Neuropathol Exp Neurol 2000; 59: 361–7.

21.

Swanson

R.A.

Farrell

Stein

B.A.

. Astrocyte energetics, function, and death under conditions of incomplete ischemia: a mechanism of glial death in the penumbra. Glia 1997; 21: 142–53.