Cataracts in the Royal College of Surgeons rat: evidence for initiation by lipid peroxidation products.
The Royal College of Surgeons (RCS) rat has been extensively studied as a model system for inherited retinal degeneration. As in a number of human retinal degenerative diseases, posterior subcapsular cataracts (PSC) are associated with the retinal changes. It has been hypothesized recently that such cataracts may be initiated by toxic products generated by the peroxidation of polyunsaturated lipid components from degenerating photoreceptor outer segments. In the present study, the possibility that such a mechanism might be responsible for cataract initiation in the RCS rat has been investigated. The degeneration of the rod outer segments (ROS) occurs rapidly in these animals, beginning a few weeks after birth. Due to the failure of the retinal pigmented epithelium to phagocytize normally, ROS degeneration is accompanied by an accumulation of debris in the eye. During the brief period of maximal debris accumulation there is a marked increase in lipid peroxidation products in the vitreous. Cataract formation is correlated temporally with these events, becoming evident immediately following the time during which peroxidation products are present in the vitreous. In addition, the primary damage detected in the RCS lenses is an increase in the passive permeability of the lens membranes. Similar lens damage has been found in studies in which normal rat lenses were exposed to degenerating ROS in vitro. These findings are consistent with the hypothesis that cataracts in the RCS rat may be initiated by toxic lipid peroxidation products.
D000375:Aging; D000818:Animals; D002386:Cataract / Q000209:etiology*; D002463:Cell Membrane Permeability; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012162:Retinal Degeneration / Q000150:complications / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013858:Thiobarbiturates / Q000378:metabolism
D008054:Lipid Peroxides; D013858:Thiobarbiturates; C029684:thiobarbituric acid