Alzheimer's and Danish dementia peptides induce cataract and perturb retinal architecture in rats

Bhanuprakash Reddy, G and Yadagiri Reddy, P and Surolia, A (2017) Alzheimer's and Danish dementia peptides induce cataract and perturb retinal architecture in rats. In: Biomolecular Concepts, 8 (1). pp. 45-54.

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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.

Item Type:	Journal Article
Publication:	Biomolecular Concepts
Publisher:	De Gruyter Open Ltd
Additional Information:	The copyright for this article belongs to Walter de Gruyter GmbH.
Keywords:	ADan; amyloid β; cataract; Danish dementia; α-crystallin
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	21 Nov 2021 16:26
Last Modified:	27 Jun 2022 09:42
URI:	https://eprints.iisc.ac.in/id/eprint/69923

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