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Anthony Nguyen, Zeljka Smit-McBride, Lawrence S Morse; Expression of the Let-7 Family of MicroRNAs in Serum of Exudative Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5784. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The let-7 family of microRNAs plays a role in angiogenesis and is implicated in several chronic diseases such as cancer. The purpose of this study is to examine the expression of the let-7 family of circulatory microRNAs in newly diagnosed wet AMD patients, comparing groups of patients sensitive and resistant to anti-VEGF therapy.
Serial blood draws over 3 months from patients that presented with newly diagnosed exudative AMD and started receiving intravitreous injections of Lucentis were collected. Blood from age-matched normals with no major ocular or systemic diseases was also collected (n=10). Patients that showed a clinical response with resolution of CME and subretinal fluid were grouped into the anti-VEGF “sensitive” group (n = 5 x 4 time points) whereas those who responded poorly (defined as persistent subretinal fluid or CME) were grouped into “resistant” groups (n=3 x 4 time points). Time points for blood draws were t = 0, 1, 2 , and 3 months. Serum RNA was isolated using modified Qiagen miRNeasy procedure, and quantitated on BioAnalyzer’s small RNA chips. Microarray miRNA analysis of serum samples was performed on samples from each group and ran on Affymetrix 3.0 miRNA arrays. Affymetrix Transcriptome Analysis Console 3.0 software was used for data normalization and ANOVA. Confirmatory quantitative real-time PCR (qPCR) was used on the select set of microRNAs for the full sample set of each group.
A significant difference was seen in the expression of the let-7 family of microRNAs in both the treatment sensitive and resistant groups compared to controls. Most notably, let-7b had the highest differential expression (FC=Fold Change; *=p<0.05) over the 3 blood draws for the sensitive group (B1 FC=77.71, B2 FC=51.63*, B3 FC=49.26*) and resistant group (B1 FC=1.01, B2 FC=34.35*, B3 FC=55.25*). Lucentis resistant patients have low let-7b expression in the initial blood draw before the start of therapy and expression increases over subsequent treatments, whereas Lucentis sensitive patients maintained an initial high expression of let-7b.
Our study suggests that levels of let-7b expression in newly diagnosed exudative AMD might be considered as a novel biomarker for resistance to anti-VEGF treatment. The let-7 family of microRNAs is known to be involved in cancer chemoresistance and further studies will elucidate its role in ocular angiogenesis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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