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Claudio Bucolo, Vincenzo Fisichella, Giovanni Giurdanella, Chiara Bianca Maria Platania, Giovanni Luca Romano, Federica Geraci, Filippo Drago; PROTECTIVE EFFECTS OF TGF-β1 AGAINST AMYLOID-β1-42 OLIGOMERS-INDUCED RETINAL DAMAGE. Invest. Ophthalmol. Vis. Sci. 2016;57(12):119.
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© 2017 Association for Research in Vision and Ophthalmology.
To set up a retinal neurodegenerative 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 (10 µM) in the presence or in the absence of recombinant human TGF-β1 (1ng/ml 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 analyses in retina lysates. Gene-pathway network analysis was carried out in order to identify which pathways are involved in AMD.
Treatment with Aβ oligomers induced a strong increase of Bax protein level (about 4-fold; p<0.01) and a significant reduction of 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. The Bcl-2 and the PI3K-Akt are the most connected nodes, for genes and pathways respectively, in the enriched gene-pathway network common to AMD and Alzheimer’s disease (AD).
These data indicate that ITV injection of Aβ1-42 oligomers in rat induces molecular changes associated with apoptotic neuronal death in retina consistent with a potential pathogenetic role of Aβ oligomers in AMD. Bioinformatics analysis confirms that apoptosis pathways are impaired in AMD. Further, these findings suggest that human recombinant TGF-β1 can prevent retinal damage elicited by Aβ oligomers.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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