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TGF-β1 prevents rat retinal insult induced by amyloid-β (1-42) oligomers.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2016 Sep 15; Vol. 787, pp. 72-7. Date of Electronic Publication: 2016 Feb 02. - Publication Year :
- 2016
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Abstract
- To set up a retinal degenerative model in rat that mimics pathologic conditions such as age-related macular degeneration (AMD) using amyloid-β (Aβ) oligomers, and assess the effect of TGF-β1. Sprague-Dawley male rats were used. Human Aβ1-42 oligomers were intravitreally (ITV) injected (10µM) in the presence or in the absence of recombinant human TGF-β1 (1ng/μl ITV injected). After 48h, the animals were sacrificed and the eyes removed and dissected. The apoptotic markers Bax and Bcl-2 were assessed by western blot analysis in retina lysates. Gene-pathway network analysis was carried out in order to identify pathways involved in AMD. Treatment with Aβ oligomers induced a strong increase in Bax protein level (about 4-fold; p<0.01) and a significant reduction in Bcl-2 protein level (about 2-fold; p<0.05). Co-injection of TGF-β1 triggered a significant reduction of Bax protein induced by Aβ oligomers. Bioinformatic analysis revealed that Bcl-2 and PI3K-Akt are the most connected nodes, for genes and pathways respectively, in the enriched gene-pathway network common to AMD and Alzheimer disease (AD). Overall, these data indicate that ITV injection of Aβ1-42 oligomers in rat induces molecular changes associated with apoptosis in rat retina, highlighting a potential pathogenetic role of Aβ oligomers in AMD. Bioinformatics analysis confirms that apoptosis pathways can take part in AMD. Furthermore, these findings suggest that human recombinant TGF-β1 can prevent retinal damage elicited by Aβ oligomers.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cytoprotection drug effects
Humans
Male
Protein Structure, Secondary
Proto-Oncogene Proteins c-bcl-2 metabolism
Rats
Rats, Sprague-Dawley
Retina cytology
bcl-2-Associated X Protein metabolism
Amyloid beta-Peptides chemistry
Amyloid beta-Peptides toxicity
Peptide Fragments chemistry
Peptide Fragments toxicity
Protein Multimerization
Retina drug effects
Transforming Growth Factor beta1 pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 787
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26845696
- Full Text :
- https://doi.org/10.1016/j.ejphar.2016.02.002