Morphological and biochemical abnormalities in a model of retinal degeneration: Canine ceroid-lipofuscinosis (CCL).

ABSTRACT

Human ceroid-lipofuscinosis is marked by blindness, dementia, ataxia, and premature death. A canine model for this disease exists in English setters whose clinical, pathological and biochemical changes resemble the human disorder. In both syndromes, autofluorescent lipopigments, i.e.; lipofuscin and ceroid ("granular", "fingerprint" and/or "curvilinear bodies") are found in the nervous system, viscera, retina, and pigment epithelium (RPE). Retinal neurons of affected animals between 6 and 22 months of age, contain a variety of abnormal intracellular pigment inclusions. Pigment epithelial cells also contain distinctive cytosomes. Electroretinograms from affected animals showed a reduction in b-wave amplitude. Leukocyte, retinal, and RPE peroxidases, were decreased in affected animals, and also showed age-related changes. In the normal canine eye, peroxidase was associated with fractions containing plasma membranes and melanolysosomes. Improved fractionation techniques localized normal peroxidase to "heavy" fractions (1.24-1.28 g/ml), and peroxidase was decreased in these fractions in CCL animals. A new particle containing hexosaminidase, galactosidase, and acid lipase was observed in affected animals. When retinal homogenates from CCL dogs were injected into the vitreous of rabbit eyes they completely abolished the ERG recording. No such change was observed with homogenates from unaffected animals. The accumulation of large numbers of dense bodies in the retina and RPE in dogs with CCL, along with a decrease in peroxidase, suggests an impairment of degradative mechanisms. Furthermore, ceroid appears to be cytotoxic to the retina and RPE. The relationship of these cytotoxic properties to the accumulation of ceroid in the eye, is the subject of our future research.