title: Alzheimer's and Danish dementia peptides induce cataract and perturb retinal architecture in rats.
abstract: Familial Danish dementias (FDDs) are autosomal dominant neurodegenerative disorders that are associated with visual defects. In some aspects, FDD is similar to Alzheimer's disease (AD)- the amyloid deposits in FDD and AD are made of short peptides: amyloid β (Aβ) in AD and ADan in FDD. Previously, we demonstrated an interaction between the dementia peptides and α-crystallin leading to lens opacification in organ culture due to impaired chaperone activity of α-crystallin. Herein, we report the in vivo effects of ADan and Aβ on the eye. ADan [reduced (ADan-red) and oxidized (ADan-oxi)] and Aβ (Aβ1-40 and Aβ1-42) were injected intravitreally in rats. The onset of cataract was seen after injection of all the peptides, but the cataract matured by 2 weeks in the case of ADan-red, 5 weeks for ADan-oxi and 6 weeks for Aβ1-40, while Aβ1-42 had minimal effect on cataract progression. The severity of cataract is associated with insolubilization and alterations in crystallins and loss of chaperone activity of α-crystallin. Further, disruption of the architecture of the retina was evident from a loss of rhodopsin, increased gliosis, and the thinning of the retina. These results provide a basis for the dominant heredo-otoophthalmo-encephalopathy (HOOE)/FDD syndrome and indicate that ADan peptides are more potent than Aβpeptides in inflicting visual impairment.
authors.affiliation: Biochemistry Division, National Institute of Nutrition, Hyderabad 500007, Telangana, India.
authors.forename: G Bhanuprakash
authors.initials: GB
authors.lastname: Reddy
authors.affiliation: Biochemistry Division, National Institute of Nutrition, Hyderabad, India.
authors.forename: P Yadagiri
authors.initials: PY
authors.lastname: Reddy
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560012, Karnataka, India.
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002524:Cerebellar Ataxia / Q000378:metabolism*; D003638:Deafness / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism; D008297:Male; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012243:Rhodopsin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D012243:Rhodopsin