Amyloid precursor protein, A beta and amyloid-associated proteins involved in chloroquine retinopathy in rats--immunopathological studies.
To understand the retinal changes in Alzheimer disease (AD) patients, pathological and immunocytochemical studies were performed on retinal cells in the chloroquine-treated rats at 0, 4, 8, 12, 16, 20, and 24 weeks after the initial injection, using anti-amyloid precursor protein (APP), -amyloid beta protein (A beta), -apolipoprotein E (apoE), -ubiquitin, and -cathepsin D antibodies. Pathological alterations consistent with chloroquine retinopathy were recognized in the ganglion cells of the ganglion cell layer (GCL) and the inner plexiform layer (IPL) 4 weeks after initial chloroquine injection. Rat retinal changes appear to have a direct relationship to the duration of chloroquine administration. Intense immunoreactivities for anti-APP, A beta, apoE (an associated protein), and ubiquitin co-localized in the swollen ganglion cells and Muller cells by 20-24 weeks together with the lysosomal enzyme cathepsin D. The present data indicate that the endosomal/lysosomal pathway plays an important role in the processing of APP in rat retina. This experimental model is considered to be a suitable neural model to understand retinal pathology and the processing of APP in terms of the pathogenesis of AD, whereas chloroquine-induced myopathy is a useful extra neuronal model.
Yoshida
T
T
Department of Neuropsychiatry, Sapporo Medical University, School of Medicine, Japan.
Fukatsu
R
R
Tsuzuki
K
K
Aizawa
Y
Y
Hayashi
Y
Y
Sasaki
N
N
Takamaru
Y
Y
Fujii
N
N
Takahata
N
N
D000682:Amyloid / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal; D002402:Cathepsin D / Q000378:metabolism; D002738:Chloroquine / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D002738:Chloroquine; D002402:Cathepsin D