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

Vincenzo Fisichella, Giovanni Giurdanella, Chiara Bianca Maria Platania, Giovanni Luca Romano, Gian Marco Leggio, Salvatore Salomone, Filippo Drago, Filippo Caraci, Claudio Bucolo

Research output: Contribution to journalArticle

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 Aβ1–42oligomers were intravitreally (ITV) injected (10 µM) in the presence or in the absence of recombinant human TGF-β1 (1 ng/μl 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 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 Aβ1–42oligomers 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.

Original languageEnglish
Pages (from-to)72-77
Number of pages6
JournalEuropean Journal of Pharmacology
Volume787
DOIs
Publication statusPublished - 2016

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Keywords

  • Alzheimer's disease
  • Macular degeneration
  • Retina
  • TGF-β1

ASJC Scopus subject areas

  • Pharmacology

Cite this

Fisichella, V., Giurdanella, G., Platania, C. B. M., Romano, G. L., Leggio, G. M., Salomone, S., Drago, F., Caraci, F., & Bucolo, C. (2016). TGF-β1 prevents rat retinal insult induced by amyloid-β (1–42) oligomers. European Journal of Pharmacology, 787, 72-77. https://doi.org/10.1016/j.ejphar.2016.02.002