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

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• 作者：Vincenzo Fisichella^a ; Giovanni Giurdanella^a ; Chiara Bianca Maria Platania^a ; Giovanni Luca Romano^a ; Gian Marco Leggio^a ; Salvatore Salomone^a ; Filippo Drago^a ; Filippo Caraci^b ; ^c ; ¹ ; Claudio Bucolo^a ; ¹ ; ^{claudio.bucolo@unict.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Macular degeneration ; Retina ; Alzheimer's disease ; TGF-β1
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：787
• 期：Complete
• 页码：72-77
• 全文大小：1875 K

文摘

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 Aβ_1–42 oligomers 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 Aβ_1–42 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.