TGF-β1 prevents rat retinal insult induced by amyloid-β (1-42) oligomers

To set up a retinal degenerative model in rat that mimics pathologic conditions such as age-related macular degeneration (AMD) using amyloid-beta (A beta) oligomers, and assess the effect of TGF-beta 1. Sprague-Dawley male rats were used. Human A beta(1-42) oligomers were intravitreally (ITV) injected (10 mu M) in the presence or in the absence of recombinant human TGF-beta 1 (1 ng/mu l ITV injected). After 48 h, 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 A beta 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-beta 1 triggered a significant reduction of Bax protein induced by A beta 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 A beta(1-42) oligomers in rat induces molecular changes associated with apoptosis in rat retina, highlighting a potential pathogenetic role of A beta oligomers in AMD. Bioinformatics analysis confirms that apoptosis pathways can take part in AMD. Furthermore, these findings suggest that human recombinant TGF-beta 1 can prevent retinal damage elicited by A beta oligomers. (C) 2016 Elsevier B.V. All rights reserved.