Alzheimer's and Danish dementia peptides induce cataract and perturb retinal architecture in rats.
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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.
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| Authors | G Bhanuprakash Reddy, P Yadagiri Reddy, Avadhesha Surolia |
| Journal | Biomolecular concepts (Biomol Concepts) Vol. 8 Issue 1 Pg. 45-84 (Mar 01 2017) ISSN: 1868-503X [Electronic] Germany |
| PMID | 28222009 (Publication Type: Journal Article, Retracted Publication) |
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