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Exp Eye Res. 2004 Nov;79(5):595-612. Related Articles, Links
Cataract formation in a strain of rats selected for high oxidative stress.
Marsili S, Salganik RI, Albright CD, Freel CD, Johnsen S, Peiffer RL, Joseph
Costello M.
Department of Cell and Developmental Biology, School of Medicine, university of
North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
The primary purpose of this study was to define the clinical and morphological
features of cataractogenesis in the OXYS strain of rats that generate excess
reactive oxygen species. Rats were sequentially examined from birth to the
development of mature cataracts with slit lamp biomicroscopy. Morphology of
selected stages of cataract development was studied using light and
transmission electron microscopy (TEM), immunohistochemical localization of the
lipid peroxidation product 4-hydroxynonenal (HNE) and fluorescent antibody
labeling for DNA oxidation products. Lenses from age-matched normal rats were
used as controls. OXYS rats developed cataracts as young as two weeks of age
with progression to maturity by 1 year. Clinically, cataracts appeared
initially either as nuclear or sub-capsular cortical changes and progressed to
pronounced nuclear cataracts within months. TEM confirmed the light microscopic
impression of region-specific alterations in both fiber cell cytoplasmic
protein matrix and membrane structure. The outer adult nuclear region showed
extensive cellular damage similar to osmotic cataracts, which is consistent
with the postulated high uptake of glucose in the OXYS strain. The adult and
outer fetal nuclear cells displayed several types of focal damage. The inner
fetal and embryonic nuclear cells demonstrated textured cytoplasm, suggesting
protein degradation or redistribution. Staining for HNE was increased in
epithelium, cortex and nucleus compared to control lenses. Fluorescent antibody
probes demonstrated increased levels of DNA oxidation products in OXYS rat
lenses compared to age-matched controls. Fourier analysis of nuclear cytoplasm
revealed significant components with corresponding sizes greater than 100 nm
and, using a new theoretical approach, the texturing of the cytoplasm was shown
to be sufficient to cause opacification of the nucleus. The OXYS rat appears to
be an ideal model for oxidative stress cataractogenesis. The potential
oxidative damage observed is extensive and characteristic of the developmental
region. The source of oxidative damage may in part be a response to elevated
levels of glucose. Because oxidative stress is thought to be a major factor in
cataract formation in both diabetic and non-diabetic aging humans, this animal
model may be a useful tool in assessing efficacy of antioxidant treatments that
may slow or prevent cataract formation.
PMID: 15500819 [PubMed - in process]
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