Biomedical subjects

K Tsuzuki

Publications and source records attributed to K Tsuzuki.

At least 37 records · Page 2Linked to original sources

PubMed2000

Influenza A virus encephalopathy with symmetrical thalamic lesions.

UNLABELLED: During an epidemic of influenza A infection in Japan, a 7-year-old boy was admitted to our hospital because of high fever, convulsions, coma, and liver dysfunction on the 2nd day of a cold-like illness. His serum CPK was markedly elevated, but there was no hyperammonaemia or hypoglycaemia. His CSF showed an increased protein level, but the cell count and glucose level were normal. CT and MRI of the brain showed symmetrical thalamic lesions, and he was diagnosed with acute necrotizing encephalopathy in childhood. He had a significant increased in antibodies to influenza A H1N1 in serum and CSF, but the CSF was negative for influenza virus using virus isolation and a polymerase chain reaction assay. CONCLUSION: Antibody production without detectable levels of influenza virus in cerebrospinal fluid suggests that virus infection occurred, but the virus did not replicate in sufficient numbers in his central nervous system. The thalamic lesion, the hallmark of acute necrotizing encephalopathy in childhood, may be initiated by a local virus infection and develop with subsequent local changes such as breakdown of the blood-brain barrier and the extravasation of blood.

Acute Disease↗

PubMed2000

Bilateral same day surgery for bilateral perforated chronic otitis media.

OBJECTIVE: Bilateral same day surgery has been performed rarely because of the risk of postoperative sensorineural hearing loss following conventional myringoplasty or tympanoplasty (CMT). Simple underlay myringoplasty (SUM) through the ear canal has been developed by Yuasa R, Saijo S, Tomioka Y, et al. Office closure of eardrum perforation with fibrin glue (in Japanese), Otolaryngol Head Neck Surg (Tokyo) 1989;61:1117-1122, which has little risk of sensorineural hearing loss. We tried bilateral same day surgery using this technique and evaluated its outcome. METHODS: Of 86 cases with bilateral perforated chronic otitis media that we treated between 1995-1997, 25 cases underwent bilateral same day surgery. Bilateral SUMs was performed on seven patients, SUM and CMT on 16 patients, and bilateral CMTs on two patients. RESULTS: Closure of perforation was successful in 18 patients (72%) on both sides and in seven patients (28%) on one side. Postoperative air-bone gap of less than 20 dB was achieved in 15 cases (60%) on both sides and in 23 cases (92%) on one side. CONCLUSION: Bilateral same day surgery for bilateral perforated chronic otitis media is possible if the operative indications are considered.

Adolescent↗

PubMed2000

A pleomorphic adenoma of the lacrimal gland in a dog.

A 13-year-old female mongrel dog had a pleomorphic adenoma of the lacrimal gland in the right upper orbit. The tumor measured 3.8 x 3.0 x 3.3 cm, appeared white, round, and firm, and pressed the right globe and surrounding tissues. Histopathologically, the tumor had a thin connective tissue capsule and was composed of tubules with two cell types, some resembling luminal epithelial cells making up the tubular structures and the other of myoepithelial cells. Epithelial tubules were disposed in an adenomatous fashion and separated from each other by proliferating pleomorphic myoepithelial cells. Immunohistochemically, large numbers of the luminal epithelial cells revealed an immunopositive reaction against keratin/cytokeratin (AE1/AE3), and some epithelial cells reacted against cytokeratin 14. Spindle-shaped myoepithelial cells revealed an immunopositive reaction against cytokeratin 14, alpha-smooth muscle actin, and vimentin. A small number of myoepithelial cells reacted against desmin. S-100 protein immunopositivity was frequently found in luminal epithelial cells and rarely in the pleomorphic myoepithelial cells. Glial fibrillary acidic protein positivity was commonly found in myoepithelial cells, myxoid matrices, and intracystic materials, but not in luminal epithelial cells.

Actins↗

PubMed1999

Selective excitation of subtypes of neocortical interneurons by nicotinic receptors.

The cellular mechanisms by which neuronal nicotinic cholinergic receptors influence many aspects of physiology and pathology in the neocortex remain primarily unknown. Whole-cell recordings and single-cell reverse transcription (RT)-PCR were combined to analyze the effect of nicotinic receptor agonists on different types of neurons in acute slices of rat neocortex. Nicotinic receptor agonists had no effect on pyramidal neurons and on most types of interneurons, including parvalbumin-expressing fast spiking interneurons and somatostatin-expressing interneurons, but selectively excited a subpopulation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin. This excitation persisted in the presence of glutamate, GABA, and muscarinic receptor antagonists and in the presence of tetrodotoxin and low extracellular calcium, suggesting that the depolarization was mediated through the direct activation of postsynaptic nicotinic receptors. The responses were blocked by the nicotinic receptor antagonists dihydro-beta-erythroidine and mecamylamine and persisted in the presence of the alpha7 selective nicotinic receptor antagonist methyllycaconitine, suggesting that the involved nicotinic receptors lacked the alpha7 subunit. Single-cell RT-PCR analysis indicated that the majority of the interneurons that responded to nicotinic stimulation coexpressed the alpha4, alpha5, and beta2 nicotinic receptor subunits. Therefore, these results provide a role for non-alpha7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical interneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism, these results also provide a cellular basis for the neuronal regulation of cortical blood flow mediated by acetylcholine.

Acetylcholine↗

PubMed1999

Expression of recombinant NMDA receptors in hippocampal neurons by adenoviral-mediated gene transfer.

N-methyl-d-aspartate (NMDA) receptors have attracted a great deal of attention because they are intimately involved in brain development, synaptic plasticity and a variety of neurological disorders. The ability to artificially alter the properties of NMDA receptors in central nervous system (CNS) neurons would be useful for elucidating the physiological roles of these receptors. It would also raise the possibility of gene therapy of neurological diseases caused by malfunction of NMDA receptors. In this study, we constructed three recombinant adenoviruses encoding rat NMDA receptor subunit cDNAs, NMDAR1 (NR1), NMDAR2B (NR2B) and mutant NR1(N598R) in which the asparagine (N) site of the wild-type NR1 was replaced with arginine (R) by site-directed mutagenesis. PC12 cells co-infected with recombinant adenoviruses bearing NR1 and NR2B cDNAs expressed conventional NMDA receptors that were permeable to Ca2+ and sensitive to Mg2+, whereas those with viruses bearing NR1(N598R) and NR2B cDNAs expressed Ca2+-impermeable and Mg2+-insensitive receptors. When rat hippocampal neurons in culture were infected with NR1(N598R) and NR2B viruses, both Ca2+ permeability and Mg2+ sensitivity of NMDA receptors were markedly reduced in the infected neurons. Excitatory postsynaptic currents (EPSCs) mediated by NMDA receptors also became much less sensitive to Mg2+. Thus, the NR1(N598R)/NR2B receptors were more dominant than the native NMDA receptors in the infected neurons, and the former receptors introduced by the adenoviral vectors functioned as postsynaptic receptors. These results indicate that the functional properties of postsynaptic NMDA receptors can be manipulated by gene transfer technology using adenoviral vectors.

Adenoviridae↗

PubMed1999

alpha-soluble N-ethylmaleimide-sensitive factor attachment protein is expressed in pancreatic beta cells and functions in insulin but not gamma-aminobutyric acid secretion.

The function of soluble N-ethylmaleimide-sensitive attachment protein-alpha (alpha-SNAP) in exocytosis still remains obscure. This study was conducted to determine the physiological role of alpha-SNAP in the secretion of insulin and gamma-aminobutryric acid (GABA) from pancreatic beta cells. Reverse transcriptase-polymerase chain reaction analysis of total RNA isolated from rat islets disclosed alpha-SNAP, but not beta-SNAP, mRNA expression, and an immunofluorescence study of rat pancreas showed that alpha-SNAP was present predominantly in the cytoplasm of the islets of Langerhans. alpha-SNAP overexpression in rat islets enhanced insulin release relative to the control levels. An in vitro binding study showed that both wild-type alpha-SNAP and C-terminal-deleted alpha-SNAP mutant (1-285) can bind to syntaxin 1A. alpha-SNAP mutant (1-285) was overexpressed to evaluate its activity as dominant-negative effector on insulin release. Overexpression of alpha-SNAP mutant (1-285) in rat islets and MIN6 cells decreased glucose-stimulated insulin release to about 50% of the control levels. Suppression of endogeneous alpha-SNAP in MIN6 cells by treatment with an antisense phosphorothioate oligonucleotide resulted in inhibition of insulin release. In order to examine if alpha-SNAP functions in exocytosis from synaptic-like microvesicles in pancreatic beta cells, the functional role of alpha-SNAP in GABA release from MIN6 cells was studied. The data showed no effect of alpha-SNAP mutant (1-285) overexpression on GABA release. We conclude that 1) alpha-SNAP plays a crucial role in insulin exocytosis via large dense core vesicles, but not GABA released via synaptic-like microvesicles, in pancreatic beta cells; and 2) the interaction of alpha-SNAP and syntaxin 1A may play an important role in the insulin exocytotic process.

Animals↗

PubMed1999

Postsynaptic expression of Ca2+-permeable AMPA-type glutamate receptor channels by viral-mediated gene transfer.

The ability to artificially express a particular receptor protein in the postsynaptic sites of neurons in the central nervous system (CNS) would be useful for the study of synaptic function of cloned receptor genes as well as for gene therapy of neurological disorders caused by dysfunction of postsynaptic receptors. In this study, we aimed to express the cDNA of unedited GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor that forms inwardly rectifying and Ca2+-permeable channel in CNS neurons by using adenoviral-mediated gene transfer. For this purpose, we have constructed a recombinant adenovirus bearing an expression-switching unit, where the unedited GluR2 cDNA can be activated by the Cre recombinase-mediated excisional deletion of a stuffer DNA interposed between the promotor and the coding region. When PC12 cells were infected with this recombinant adenovirus together with an adenovirus expressing Cre recombinase, the inwardly rectifying and Ca2+-permeable AMPA receptor channels were expressed in nearly 100% of infected cells. Two days after co-infection of cultured rat hippocampal neurons with these adenoviruses, fast excitatory neurotransmission in the glutamatergic synapse was mediated predominantly by the inwardly rectifying and Ca2+-permeable AMPA receptor channels. This indicates that the native AMPA receptors in the postsynaptic sites of the glutamatergic synapse are replaced rapidly with recombinant receptors newly produced by the viral-mediated gene transfer.

2-Amino-5-phosphonovalerate↗

PubMed1999

Structure-activity study of intact porcine motilin.

Biologically important sites on intact porcine motilin (pMTL) were explored using its partial peptides. The partial peptides were synthesized using Fmoc (9-fluorenylmethyloxycarbonyl) solid phase methodology, and tested for the binding activity to motilin receptor and the smooth muscle contractile activity. The results were as follows: important residues for the contractile activity were found to be Phe1, Ile4, and Tyr7, and an open space existed beyond the N-terminus between motilin and its receptor. On the model of interaction between motilin and motilin receptor evolved from these results, the three points of interaction, due to Phe1, Ile4, and Tyr7, and the presence of an open space were expected. The motilin agonist and antagonist, designed on this model, will help the inquiry into motilin associated diseases.

Amino Acid Sequence↗

PubMed1999

Interobserver errors in anthropometry.

To present basic information on the interobserver precision and accuracy of 32 selected anthropometric measurement items, six observers measured each of 37 subjects once in two days. The data were analyzed by using ANOVA, and mean absolute bias, standard deviation of bias, and mean absolute bias in standard deviation unit were used as measures of bias. By comparing the results of the two days, the effects of the practice on measurement errors were also investigated. Variance was overestimated by more than 10% in five measurements. Interobserver error variance and random error variance were highly correlated with each other. Measures of the bias were significantly correlated with interobserver and especially with random error variances. The interobserver errors were drastically reduced on the second day in the measurement items in which the causes of the interobserver errors could be specified. It was speculated that even when the definitions of the landmarks and measurement items were clear, the ambiguity in the practical procedures in locating landmarks, applying instruments, and so on, permitted each observer to develop his or her own measurement technique, and it in turn caused interobserver errors. To minimize interobserver and random errors, the standardization of measurement technique should be extended to the details of the practical procedures.

Adult↗

PubMed1998

Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's disease-affected brain.

Presenilin-1 (PS-1) has been identified as the protein encoded by the chromosome 14 locus that, when mutated, leads to familial Alzheimer's disease (FAD). The role PS-1 plays in the pathogenesis of Alzheimer's disease (AD) remains unclear. Using a set of antibodies raised against PS-1 synthetic peptides, polyclonal antibody to amyloid beta protein (Abeta) and end-specific antibodies against Abeta40, and Abeta42, immunohistochemical studies were performed on brain sections obtained from AD cases and controls. The PS-1 antibodies clearly stained amyloid angiopathies in AD-affected brains, but no recognizable immunoreactions were observed in any other vessels free from amyloid involvement in either AD-affected brains or controls. Abeta antibodies and the end-specific antibody against Abeta40 also decorated amyloid angiopathies, showing localization similar to that of PS-1. Western blot analyses predominantly detected protein band polypeptide species of a 50 kDa, band, presumably full-length PS-1 protein with N-terminus antisera, since these antibodies turned out to recognize a 50-kDa full-length band in cell lysate of transfected HeLa cell overexpressing PS-1. In addition, we recognized 30, 27 and 25 kDa proteins in both AD and control brain homogenate with these antibodies. In microvessel fractions extracted from brain homogenates, the 50, and 27 kDa fragments were observed in AD-affected brains but not in those of controls. C-terminus rabbit antisera reacted strongly with the 33 and 27 kDa bands, and additionally detected a small amount of full-length PS-1 protein in extracts from AD and control brains. Our present data indicate that PS-1 might be involved in the pathogenesis of amyloid angiopathy in the AD brain.

Alzheimer Disease↗

PubMed1998

Advanced glycation end products in Alzheimer's disease and other neurodegenerative diseases.

Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but A beta negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.

Adult↗

PubMed1998

Glutamate receptors in the mammalian central nervous system.

Glutamate receptors (GluRs) mediate most of the excitatory neurotransmission in the mammalian central nervous system (CNS). In addition, they are involved in plastic changes in synaptic transmission as well as excitotoxic neuronal cell death that occurs in a variety of acute and chronic neurological disorders. The GluRs are divided into two distinct groups, ionotropic and metabotropic receptors. The ionotropic receptors (iGluRs) are further subdivided into three groups: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptor channels. The metabotropic receptors (mGluRs) are coupled to GTP-binding proteins (G-proteins), and regulate the production of intracellular messengers. The application of molecular cloning technology has greatly advanced our understanding of the GluR system. To date, at least 14 cDNAs of subunit proteins constituting iGluRs and 8 cDNAs of proteins constituting mGluRs have been cloned in the mammalian CNS, and the molecular structure, distribution and developmental change in the CNS, functional and pharmacological properties of each receptor subunit have been elucidated. Furthermore, the obtained clones have provided valuable tools for conducting studies to clarify the physiological and pathophysiological significances of each subunit. For example, the generation of gene knockout mice has disclosed critical roles of some GluR subunits in brain functions. In this article, we review recent progress in the research for GluRs with special emphasis on the molecular diversity of the GluR system and its implications for physiology and pathology of the CNS.

Animals↗

PubMed1998

Diagnosis of the nutcracker phenomenon using two-dimensional ultrasonography.

We aimed to establish new criteria for the diagnosis of the nutcracker phenomenon (N phenomenon) using ultrasonography (US). The left renal vien (LRV) was examined with US in 125 children, divided into three groups, namely the macroscopic hematuria group (23 children), the microscopic hematuria group (52 children) and the control group (50 normal children) all without nephritis, urolithiasis and tumor. The following parameters were calculated: (1) the ratio of the diameter of the dilated part of the LRV (D) to that of the narrowed part of the same vein (N) (D/N ratio), (2) the ratio of D to the aortic diameter (A) (D/A ratio) and (3) the difference in diameter between the LRV and the right renal vein (RRV) (RVD difference). The D/A ratio and the RVD difference correlated significantly with the D/N ratio. This indicates that not only the D/N ratio but also the D/N ratio but also the D/A ratio and RVD difference can be used for diagnosing the N phenomenon. The cutoff levels for the three parameters were set at the mean + 2 SD of the values of the normal controls, that is, at 3.7 (D/N ratio), 0.75 (D/A ratio) and 1.7 mm (RVD difference). We made diagnoses of the N phenomenon when two or more parameters were over the cutoff level. According to these criteria, most patients with macrohematuria and one third of patients with microhematuria were positive for the N phenomenon. The D/A ratio and RVD difference were useful for diagnosing the N phenomenon, and as a result our criteria can reduce misdiagnosis for normal children.

Adolescent↗

PubMed1998

[Analysis of molecular basis of neuronal properties using the patch-clamp RT-PCR method].

The AMPA-type glutamate receptor mediates fast neurotransmission in most of the excitatory synapses in the brain. Expression studies of the AMPA receptor subunits, GluR1-GluR4, have shown that the functional properties of AMPA receptors, such as rectification and Ca2+ permeability, are determined by their subunit composition. To analyze the molecular basis of functional properties of AMPA receptors at the single neuron level, we have combined the whole-cell patch clamp recording with the reverse transcription-polymerase chain reaction (patch-clamp RT-PCR method). Using this method, we have demonstrated that expression of the GluR2 subunit determines rectification properties and Ca2+ permeability of AMPA receptors in different types of neurons. The patch-clamp RT-PCR technique will be useful for a wide range of physiological studies to elucidate the molecular basis of functional properties at the single cell level.

Animals↗

PubMed1997

Molecular cloning and characterization of human keratan sulfate Gal-6-sulfotransferase.

We have previously cloned chondroitin 6-sulfotransferase (C6ST) cDNA from chick embryo chondrocytes. C6ST catalyzes sulfation of chondroitin, keratan sulfate, and sialyl N-acetyllactosamine oligosaccharides. In this study, we report the cloning and characterization of a novel sulfotransferase that catalyzes sulfation of keratan sulfate. This new sulfotransferase cDNA clone was obtained from a human fetal brain library by cross-hybridization with chick C6ST cDNA. The cDNA clone obtained contains a single open reading frame that predicts a type II transmembrane protein composed of 411 amino acid residues. When the cDNA was introduced into a eukaryotic expression vector and transfected in COS-7 cells, keratan sulfate sulfotransferase activity was overexpressed, but C6ST activity was not increased over that of the control. Structural analysis of 35S-labeled glycosaminoglycan, which was formed from keratan sulfate by the reaction with 35S-labeled 3'-phosphoadenosine 5'-phosphosulfate and the recombinant sulfotransferase, showed that keratan sulfate was sulfated at position 6 of Gal residues. On the basis of the acceptor substrate specificity, we propose keratan sulfate Gal-6-sulfotransferase (KSGal6ST) for the name of the newly cloned sulfotransferase. KSGal6ST was assigned to chromosome 11p11. 1-11.2 by fluorescence in situ hybridization. Among various human adult tissues, a 2.8-kilobase message of KSGal6ST was expressed mainly in the brain. When poly(A)+ RNAs from the chick embryo cornea and brain were probed with the human KSGal6ST cDNA in Northern hybridization, a clear band with about 2.8 kilobases was detected. These observations suggest that KSGal6ST may participate in the biosynthesis of keratan sulfate in the brain and cornea.

Amino Acid Sequence↗

PubMed1997

Adenovirus-mediated expression of AMPA-type glutamate receptor channels in PC12 cells.

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor channels are expressed ubiquitously in brain neurons and mediate fast excitatory neurotransmission. They are composed of four subunits, GluR1, GluR2, GluR3 and/or GluR4. We constructed recombinant adenoviruses encoding rat AMPA receptor subunit cDNAs, GluR1 (AxCAGluR1) and silently mutated GluR2 (AxCAGluR2X) with modified chicken beta-actin promoter and cytomegalovirus immediate-early enhancer. Using these adenoviral vectors, we transferred the GluR1 and GluR2 genes into PC12 cells that possess no functional AMPA receptor channels. PC12 cells infected with these viruses expressed GluR1 and GluR2 RNAs. Immunoblot analysis indicated that the expressed GluR1 and GluR2 proteins were equivalent to those of the rat brain. Functional expression of the AMPA receptor channels was examined using the whole-cell patch clamp technique. In AxCAGluR1-infected cells, the current-voltage (I-V) relationship of response to kainate, a non-desensitizing agonist of AMPA receptors, exhibited a strong inward rectification, indicating the formation of functional GluR1-homomeric channels. In cells infected with both AxCAGluR1 and AxCAGluR2X, the I-V relationship of kainate responses exhibited an outward rectification, indicating the formation of heteromeric GluR1/R2 channels. Immunocytochemical analysis revealed that the AMPA receptor subunit genes were transferred in more than 95% of the infected PC12 cells.

Adenoviridae↗

PubMed1997

Amino-terminus truncated apolipoprotein E is the major species in amyloid deposits in Alzheimer's disease-affected brains: a possible role for apolipoprotein E in Alzheimer's disease.

Amyloid deposits in Alzheimer's disease (AD) are composed of amyloid beta protein (A beta) and many other components called amyloid-associated proteins. Apolipoprotein E (apoE) is one of the most important amyloid-associated proteins. The role apoE plays in AD, however, is yet to be determined. In this study, we present the biochemical and histochemical nature of apoE in AD-affected brains using four monoclonal antibodies (mAbs) against apoE and newly established antibodies against the amino-terminal (anti-apoE-N), and carboxyl-terminal regions (anti-apoE-C) of apoE. Competitive ELISA and Western-blot analysis combined with thrombolytic digestion of apoE indicated that our four mAbs recognized at least two different epitopes within a 22-kDa amino-terminal domain of apoE. Using these mAbs and an anti-A beta mAb, double immunostaining showed that the majority of amyloid deposits were stained by both anti-apoE and anti-A beta mAbs, but the minority of them were detected only by either anti-apoE or anti-A beta mAbs. Differences in staining properties between anti-apoE-N and anti-apoE-C were that anti-apoE-C recognized both amyloid deposits and astrocytes similar to anti-apoE mAbs, but anti-apoE-N strongly stained only astrocytes. Preliminary semi-quantitative determinations of apoE in CSF and brain homogenate showed that the amount of apoE increased in AD and Creutzfeldt-Jakob disease brains compared to normal samples. Our immunological data, using antibodies specific for the amino and carboxyl termini of apoE, suggest that apoE may, in some circumstances, initiate plaque formation, and that apoE in amyloid deposits has at least part of its amino termini cleaved out.

Alzheimer Disease↗

PubMed1997

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.

Amyloid↗