MicroRNA Expression Patterns Involved in Amyloid Beta–Induced Retinal Degeneration

Abstract

Citation: Huang P, Sun J, Wang F, et al. MicroRNA expression patterns involved in amyloid beta-induced retinal degeneration. Invest Ophthalmol Vis Sci. 2017;58:172658: -173558: . DOI: 10.1167 PURPOSE. Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (Ab) is speculated to be one of the key pathologic factors. While the detrimental effects of Ab on retinas have been widely explored, Ab-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an Ab-induced mouse model of retinal degeneration.METHODS. C57BL/6 mice were intravitreally injected with Ab 1-40 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 Ab 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 Ab accumulation could lead to relevant biochemical alternations such as complement activation, barrier impairment, apoptosis, and positive feedback of Ab production.

Cooperation of Rel family members in regulating Aβ1-40-mediated pro-inflammatory cytokine secretion by retinal pigment epithelial cells

“…Our prior study showed that RPE cells from A β 1-40 -injected mice displayed hyper- and hypopigmentation. 21 In the current study, the structure and function of the retina were evaluated by TEM and ERG, respectively. The ultrastructural alterations and decreased ERG responses observed in our study were similar to those reported in other AMD animal models.…”

FTO alleviates Aβ1-40 induced retinal pigment epithelium degeneration via PKA/CREB signaling pathway

“…Human AMD samples displayed signi cant inter-individual variation in RPE transcript expression [5], supporting that heterogenic stress responses underlie AMD pathological process. C57BL/6 mice intravitreally injected with Amyloid-β 1−40 (Aβ 1−40 ) showed degenerative changes and apoptosis within the retina, and microRNAs (mi-RNAs) expression pro ling proved differential expression of miRNAs between the Aβ model and the control group [6]. However, these ndings cannot fully explain the data obtained from other researches.…”

Epigenetics in age-related macular degeneration: new discoveries and future perspectives

“…Haematoxylin and eosin-stained sections of retinal pigment epithelium (RPE)/neural retina tissue of C57BL/6 mice intravitreally injected with Ab1-40 or PBS showed degenerative changes, and immunofluorescence testing demonstrated apoptosis within the retina after Ab1-40 injection [96]. In the same study, miRNA expression profiling proved differential expression of miRNAs between the Ab model and the control group.…”