Ocular pathology in mitochondrial superoxide dismutase (Sod2)-deficient mice.
OBJECTIVE
To characterize the pathologic features in retina, optic nerve, and extraocular muscle of mitochondrial superoxide dismutase (Sod2)-deficient mice, a model of increased mitochondrial production of reactive oxygen species.


METHODS
Morphometric and ultrastructural study of eyes of 43 homozygous sod2(tm1Cje-/-) mice and wild-type control animals. For retinal morphometric analysis, 32 manganese 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP)-treated animals aged either 9 to 10 days or 20 to 21 days were studied. Ultrastructural examination was performed on tissue from the treated animals, and 11 additional untreated mutant and control animals.


RESULTS
In treated Sod2-deficient animals, the photoreceptor layer was thinner centrally at 9 to 10 days than in control animals (mean 8.8 vs. 14.7 microm). By 20 to 21 days, all retinal layers apart from the outer nuclear layer and retinal pigment epithelium (RPE) were thinner centrally in mutant animals (total retinal thickness, 233.2 vs. 272.6 microm; combined nerve fiber layer, ganglion cell layer, and inner plexiform layer, 86.2 vs. 103.4 microm; inner nuclear layer, 51.8 vs. 60.3 microm; photoreceptors, 26.7 vs. 35.6 microm). Optic nerve cross-sectional area was less in 20- to 21-day-old treated Sod2-deficient animals than in control animals. Mitochondrial morphologic abnormalities (swelling, pale matrix, and disorganized cristae) were found predominantly in older mutant animals' (16 and 20 to 21 days) RPE and in extraocular muscle of a 16-day-old untreated mutant.


CONCLUSIONS
In sod2(tm1Cje-/-) mice, there is relative progressive retinal thinning, with particular involvement of the inner retinal layers and an early effect on the photoreceptor layer, as well as mitochondrial morphologic abnormalities, all consistent with mitochondrial disease.
Sandbach
J M
JM
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, USA.
Coscun
P E
PE
Grossniklaus
H E
HE
Kokoszka
J E
JE
Newman
N J
NJ
Wallace
D C
DC
D000818:Animals; D016166:Free Radical Scavengers / Q000627:therapeutic use; D008665:Metalloporphyrins / Q000627:therapeutic use; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D009801:Oculomotor Muscles / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D009901:Optic Nerve Diseases / Q000201:enzymology / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012164:Retinal Diseases / Q000201:enzymology / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000172:deficiency*
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013482:Superoxide Dismutase