Purpose: Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (Aβ) is speculated to be one of the key pathologic factors. While the detrimental effects of Aβ on retinas have been widely explored, Aβ-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an Aβ-induced mouse model of retinal degeneration.
Methods: C57BL/6 mice were intravitreally injected with Aβ1-40 or PBS and the eye tissues were collected for hematoxylin and eosin (H&E) staining, apoptosis immunofluorescence staining, and miRNA profiling. After filtering, 10 miRNAs and their target genes were chosen for quantitative RT-PCR (qRT-PCR) confirmations. Pathway analyses were employed for further bioinformatic analyses.
Results: Hematoxylin and eosin-stained sections of retinal pigment epithelium (RPE)/neural retina tissue demonstrated degenerative alterations, and immunofluorescence testing revealed apoptosis within the retina after Aβ treatments. MicroRNA profiling revealed 61 miRNAs that were differentially expressed between the model and the control group. Among these, 38 miRNAs were upregulated (fold change > 1.5, P < 0.05) and 23 miRNAs were downregulated (fold change < 0.667, P < 0.05). Five of the 10 selected miRNAs (miR-142, miR-216, miR-155, miR-223, and miR-433) as well as several key target genes (CFH, IGF-1R, c-MET, and ABCA1) were confirmed by qRT-PCR analyses.
Conclusions: Our study is the first to profile the miRNA expression patterns and suggests that Aβ accumulation could lead to relevant biochemical alternations such as complement activation, barrier impairment, apoptosis, and positive feedback of Aβ production.