Ocular pathology in mitochondrial superoxide dismutase (Sod2)-deficient mice

PURPOSE. To characterize the pathologic features in retina, optic nerve, an d extraocular muscle of mitochondrial superoxide dismutase (Sod2)-deficient mice, a model of increased mitochondrial production of reactive oxygen spe cies. METHODS. Morphometric and ultrastructural study of eyes of 43 homozygous so d2(tmlCje-/-) mice and wild-type control animals. For retinal morphometric analysis, 32 manganese 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTB AP)-treated animals aged either 9 to 10 days or 20 to 21 days were studied. Ultrastructural examination was performed on tissue from the treated anima ls, and 11 additional untreated mutant and control animals. RESULTS. In treated Sod2-deficient animals, the photoreceptor layer was thi nner centrally at 9 to 10 days than in control animals (mean 8.8 vs. 14.7 m um). By 20 to 21 days, all retinal layers apart from the outer nuclear laye r and retinal pigment epithelium (RPE) were thinner centrally in mutant ani mals (total retinal thickness, 233.2 vs. 272.6 mum; combined nerve fiber la yer, ganglion cell layer, and inner plexiform layer, 86.2 vs. 103.4 mum; in ner nuclear layer, 51.8 vs. 60.3 mum; photoreceptors, 26.7 vs. 35.6 mum). O ptic nerve cross-sectional area was less in 20- to 21-day-old treated Sod2- deficient animals than in control animals. Mitochondrial morphologic abnorm alities (swelling, pale matrix, and disorganized cristae) were found predom inantly in older mutant animals' (16 and 20 to 21 days) RPE and in extraocu lar 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 e arly effect on the photoreceptor layer, as well as mitochondrial morphologi c abnormalities, all consistent with mitochondrial disease.