title: TGF-β1 prevents rat retinal insult induced by amyloid-β (1-42) oligomers.
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.
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors: Vincenzo
authors: V
authors: Fisichella
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors: Giovanni
authors: G
authors: Giurdanella
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors: Chiara Bianca Maria
authors: CB
authors: Platania
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors: Giovanni Luca
authors: GL
authors: Romano
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors: Gian Marco
authors: GM
authors: Leggio
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors: Salvatore
authors: S
authors: Salomone
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors: Filippo
authors: F
authors: Drago
authors: Department of Drug Sciences, University of Catania, Catania, Italy; IRCSS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors: Filippo
authors: F
authors: Caraci
authors: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy. Electronic address: claudio.bucolo@unict.it.
authors: Claudio
authors: C
authors: Bucolo
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D053773:Transforming Growth Factor beta1; C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein
keywords: Alzheimer's disease; Macular degeneration; Retina; TGF-β1